Department of Analytical Chemistry
Research group Atomic and Mass Spectrometry
Interference-free determination of ultra-trace levels of
Arsenic and Selenium using methyl fluoride as
reaction gas in ICP-MS/MS
Thesis submitted to obtain
the degree of Master of Science in Chemistry by
Elisabeth Nissen
Academic year 2013 - 2014
Promoter: Prof. Dr. Frank Vanhaecke
Copromoter: Dr. Lieve Balcaen
Supervisor: Eduardo Bolea-Fernandez
Acknowledgements/preface
During the academic year 2013/2014, Master student Elisabeth Nissen has produced the following
Master thesis to obtain the degree of Master of Science in Chemistry. All lab work was performed
from September 2013 to May 2014 at the Department of Analytical Chemistry, Atomic and Mass
Spectrometry group, Ghent University. It is expected that the reader has a basic knowledge of
analytical chemistry.
A great thanks to the staff and students at the Department of Analytical Chemistry, Atomic and
Mass Spectrometry group, Ghent University, for supplying the instrumentation, facilities and help
to execute this Master thesis project. I especially owe PhD student Eduardo Bolea-Fernandez, Dr.
Lieve Balcaen and Prof. Dr. Frank Vanhaecke a great thanks, since their help was invaluable in the
execution of this Master thesis project.
Abbreviations
AAS
Atomic absorption spectrometry
AFS
Atomic flourescence spectrometry
ICP-AES
Inductively coupled plasma-atomic emission spectrometry
ICP-MS
Inductively coupled plasma-mass spectrometry
LOD
Limit of detection
LOQ
Limit of quantification
SF-ICP-MS
Double-focusing sector field ICP-MS
Q-ICP-MS
Quadrupole ICP-MS
ICP-MS/MS
Tandem mass spectrometry ICP-MS
CH3F
Methyl fluoride
DCP
Direct current plasma
MIP
Microwave induced plasma
IP
Ionization potential
m/z-ratio
Mass-to-charge ratio
ESA
Electrostatic analyzer
TOF
Time of flight
Q1
1st Quadrupole
Q2
2nd Quadrupole
MS/MS set-up
Q1 followed by a collision/reaction cell and Q2
SQ set-up
Collision/reaction cell followed by a single quadrupole
MFC
Mass flow controller
Overview
1. Introduction and aim...................................................................................................................................... 1
2. Theory............................................................................................................................................................ 6
2.1 Instrumentation ........................................................................................................................................ 6
2.1.1 ICP-MS in general ............................................................................................................................ 6
2.1.2 Interferences in ICP-MS ................................................................................................................. 13
2.1.3 Triple quadrupole mass spectrometry (ICP-MS/MS) ..................................................................... 14
2.2 Contamination ....................................................................................................................................... 18
3. Experimental................................................................................................................................................ 19
3.1 Instrumentation ...................................................................................................................................... 19
3.2 Samples and reagents ............................................................................................................................ 21
3.3 Sample preparation ................................................................................................................................ 22
3.3.1 Digestion procedure........................................................................................................................ 22
3.3.2 Reconstitution procedure for urine ................................................................................................. 23
4. Results and discussion ................................................................................................................................. 25
4.1 Optimization of ICP-MS/MS protocol for the determination of As and Se .......................................... 25
4.1.1 As.................................................................................................................................................... 25
4.1.2 Se .................................................................................................................................................... 30
4.2 Optimization of SF-ICP-MS protocol for the determination of As and Se ........................................... 36
4.3 Calibration data and limits of detection ................................................................................................. 37
4.3.1 As.................................................................................................................................................... 37
4.3.2 Se .................................................................................................................................................... 39
4.4 Investigation of the improvement in sensitivity by the addition of MeOH ........................................... 40
4.4.1 As.................................................................................................................................................... 40
4.4.2 Se .................................................................................................................................................... 42
4.5 Results obtained for simulated matrices ................................................................................................ 44
4.5.1 As.................................................................................................................................................... 44
4.5.2 Se .................................................................................................................................................... 47
4.6 Results obtained for reference materials - As and Se ............................................................................ 52
5. Conclusion ................................................................................................................................................... 56
6. References ................................................................................................................................................... 57
7. Appendix ..................................................................................................................................................... 61
1. Introduction and aim
Arsenic (As) and selenium (Se) are two interesting elements to investigate, due to their presence in
different sample types e.g., environmental and biological samples, and due to the fact that As is
known to be a toxin, whereas Se is an essential element, but it becomes toxic at higher
concentrations, while the difference between an appropriate and an excessive concentration is
small.[1, 2]
Arsenic is a metalloid, which is present in the environment through both a natural route, with an
abundance in the earth's crust of 2.5 μg/g, and an anthropogenic route due to industrial, agricultural
and mining activities.[3,4] Arsenic is present in both organic and inorganic forms and in various
oxidation states (-III, 0, +III, +V). The toxicity is related to its chemical form and oxidation state
and inorganic species are known to be more toxic than organic species, with decreasing toxicity for
the species as follows: arsenite > arsenate > monomethylarsonate (MMA) > dimethylarsinate
(DMA).[1,2,5,6] For a human adult, inorganic As is lethal at an amount of 1 - 3 mg As/kg, whereas
long term exposure to inorganic As has been linked to adverse effects such as skin lesions, cancer,
developmental toxicity, cardiovascular diseases, neurotoxicity, abnormal glucose metabolism and
diabetes.[5]
Selenium is a non-metal, which is also present in the environment naturally, with an abundance in
the earth's crust of 0.05 μg/g, but it is also introduced through anthropogenic routes similar to those
of As, as a result of agriculture, mining, petrochemical and industrial activities.[7] Selenium also
exists in both organic and inorganic forms and in different oxidation states (+VI, +IV, 0, -II), and in
the environment, Se species such as Se (IV), Se (VI), dimethylselenide (dMeSe),
dimethyldiselenide (dMedSe) and dimethylselenone (dMeSeO2) can be found, with organic and
inorganic species having different toxicity. As mentioned before, Se is an essential element and it
can be linked to biological activities such as antioxidant actions, activation and degradation of
thyroid hormones, immunity enhancement, and reduction of colon cancer risk. However for Se, the
range between the deficiency level (< 40 μg/day for adults) and the toxic level (> 400 μg/day for
adults) is very narrow. A deficit in Se has been linked to some endemic diseases and the exposure to
too much Se can lead to selenosis.[2,8,9]
Page 1 of 65
Due to As being toxic even at low levels and the fact that for Se the range between toxic or essential
is very narrow and at low levels, it is important to be able to determine As and Se at ultra-trace
levels with high accuracy.
Arsenic and selenium have been investigated earlier using a variety of analytical techniques, such as
atomic absorption spectrometry (AAS)[10-12], atomic flourescence spectrometry (AFS)[13-15] and
inductively coupled plasma-atomic emission spectrometry (ICP-AES)[16-18]. However, inductively
coupled plasma-mass spectrometry (ICP-MS) has to be considered as the technique of choice due to
the advantages of very low limits of detection (LOD), a wide linear dynamic range, as well as
multi-element and isotopic capabilities.[1,2,19-22] However, the determination of As and Se within a
complex matrix by means of ICP-MS is not that straightforward, due to the following reasons: 1)
both As and Se have high ionization energies (9.82 eV and 9.75 eV, respectively), which means that
they are poorly ionized under normal ICP-MS conditions, and the ionization efficiency is in the
order of 52 % and 33 %, respectively[23], leading to poor sensitivity for the elements, and 2) spectral
overlap occurs for As and all Se - isotopes (Table 1) as a result of the occurrence of e.g., isobaric,
polyatomic and doubly charged ions of the same m/z-ratios, which means that interference-free
determination is a challenge.
Table 1 As and Se - isotopes with their natural isotopic abundance[24] and the most important isobaric, polyatomic and
doubly charged interferences[25,26] (non-restrictive list).
Analyte
75
Abundance
(%)
Isobaric
interference
100
-
As+
Doubly charged
interference
Polyatomic interference
40
74
Se+
0.89
74
Ge+
76
Se+
9.37
76
Ge+
-
77
Se+
7.63
78
Se+
23.77
78
Kr+
80
Se+
49.61
80
Kr+
82
Se+
8.73
82
Kr+
Ar35Cl+, 59Co16O+, 36Ar38ArH+, 38Ar37Cl+, 36Ar39K+,
43
Ca16O2+, 40Ar 23Na12C+, 12C31P16O2+, 40Ca35Cl+
37
150
Nd2+,150Eu2+,150Sm2+
Cl37Cl+, 36Ar38Ar+, 38Ar36S+, 40Ar34S+, 39K35Cl+,
58
Ni16O+
148
Ar36Ar+, 38Ar38Ar+, 60Ni16O+, 39 K37Cl+, 41K35Cl+
152
40
38
39
+ 61
16
+ 59
18
+ 40
37
+ 40
37
Ar K , Ni O , Co O , Ar Cl , Ca Cl
36
Ar40ArH+, 38Ar2H+, 12C19F14N16O2+
+
38
Sm2+, 148Nd2+
Sm2+, 152Gd2+
154
Sm2+, 154Gd2+
Ar 40Ca+, 62Ni16O+, 41K37Cl+, 40Ar 38Ar+
156
Ar 40Ca+, 64Ni16O+, 64Zn16O+, 32S216O+, 32S16O3+,
40
Ar40Ar+, 40Ca40Ca+,
160
Ar 42Ca+,34S16O3+,
164
40
40
66
Zn16O+, 12C35Cl2+, 40Ar2H2+
Gd2+, 156Dy2+
Gd2+, 160Dy2+
Dy2+, 164Er2+
In literature, a variety of different approaches have been suggested to deal with these problems.
With regard to the problem of poor ionization, several studies have used the addition of organic
solvents, such as ethanol or methanol, or organic compounds to induce a signal enhancement of
these elements, denoted the carbon effect. The presence of carbon in a sample can influence the
ionization conditions in the plasma, the rate at which the aerosol is transported, the nebulization
Page 2 of 65
efficiency for the sample and/or the mass load of vapor. The signal enhancement is due to an
alteration of the region of maximum ion density in the plasma, an enhancement of the nebulization
of the sample and due to a charge transfer reaction from C+ species to analyte ions: C+ + M → M+ +
C-species (1), where M is the analyte ion. This signal enhancement is especially observed for some
species, such as As and Se, so-called hard-to-ionize elements, since carbon has an even higher
ionization energy of 11.36 eV, and it can transfer its positive charge according to process (1).[23,27]
In literature, studies can be found that report an enhancement of the As signal of 240 % and of the
Se signal of 250 % due to the presence of glycerol, and as a results of methane being present an
enhancement of 500 % and 300 % for As and Se, respectively, was reported[28], whereas other
papers have also reported an enhancement of 150 % for As and Se using methanol[21]. However, if
the presence of carbon affects the total intensity of As and Se in a sample, this can also cause a
problem, since standards and samples may have a different C-content, and then, external calibration
fails. Thus, it is important to use an appropriate internal standard to correct for this enhancement,
thus one that also experiences this carbon effect or use standard addition for calibration.[29]
In order to overcome the problem of spectral interference, two main approaches have been
proposed. 1) Using a quadrupole-based ICP-MS instrument (Q-ICP-MS) equipped with a
collision/reaction cell to overcome the problem of spectral interference by chemical resolution,
where either the interference is removed or reduced due to collision or reaction with the cell gas or
where the analyte reacts with the cell gas and forms a reaction product that can be measured
interference-free at another m/z-ratio.[22] By using a collision gas mixture, such as H2/He, one can
aim at reducing the spectral background at the mass of As and at the masses of the Se - isotopes.
However, this will also substantially reduce the transmission of As+ and Se+ ions. Detection limits
of 0.15 μg/L and 0.03 μg/L have been reported for As and Se (via
80
Se), respectively, using this
method.[19] Another option is to use a reaction gas such as O2, in order to convert As+ and Se+ ions
into AsO+ and SeO+ ions, and measure in the mass-shift mode, where the reaction product can be
detected at the new mass (m/z 91 for 75As+ and m/z 90, 92, 93, 94, 96 and 98 for 74Se+, 76Se+, 77Se+,
78
Se+, 80Se+ and 82Se+, respectively).[30,31] Other typical gases that could be used, are CH4 and H2.[32]
2) A second option is to use an ICP-MS instrument equipped with a double-focusing sector field
mass analyzer, denoted SF-ICP-MS, where the mass resolution is high enough for interference-free
determination. However, this instrument comes at a high purchase price and the use of the high
resolution mode results in the loss of sensitivity of 2 orders of magnitude, due to a reduction in the
Page 3 of 65
transmission efficiency of the ions, which results in a reduction of the signal intensity.[22] Detection
limits of 0.004 μg/L[33] and 0.004 μg/L[34] have been reported for As and Se (via 82Se), respectively,
using this technique. Typically SF-ICP-MS is the method of choice for ultra-trace level
determination of As and Se, since it offers the best limits of detection.
In 2013, a new generation of quadrupole-based ICP-MS instrumentation was introduced. This new
generation of instruments is based on a triple quadrupole (ICP-QQQ) set-up, where an octopolebased collision/reaction cell is placed in-between two quadrupole mass analyzers. This allows for
the operation of the ICP-MS/MS instrument in MS/MS mode, which should be able to deal better
with spectral overlap. The improvement is mainly due to the introduction of the first quadrupole
before the collision/reaction cell, which only lets the analyte and other on-mass ions pass. Thus, the
reactions in the cell are more under control, and additionally, the new set-up makes it possible to
perform a product ion scan, which can be used to easily identify which products are formed.[22] This
opens up the possibility to potentially be able to match the detection limits obtained using SF-ICPMS (or maybe even obtain better detection limits). As an example, in literature it can be found, that
in a study on the determination of titanium in blood, using ICP-MS/MS and NH3/He as reaction
gas, instrumental detection limits were found equal to those obtained by SF-ICP-MS.[35]
Typical gases used for ICP-MS/MS are H2, He, NH3, O2 or a mixture of these. However in this
project, a rather unconventional reaction gas, methyl fluoride (CH3F), is investigated for the use in
determining As and Se at ultra-trace levels. In the literature, it can be found that CH3F has been
used before as reaction gas, e.g., in determining the 87Sr/86Sr isotope ratio in magmatic rocks, which
suffers from the isobaric interference of
87
Rb+ and good results were obtained[36] or in order to
conduct isotope-dilution determination of vanadium (50V+,
interferences from
50
Ti+ and
50
51
V+), where 50V+ suffers from isobaric
Cr+, and it was shown that with a mixture of CH3F and NH3 as
reaction gas, it was possible to reduce the isobaric interferences[37].
In a study conducted by Xiang Zhao et al, it was investigated which kind of reactions CH3F had
with atomic transition - metal and main - group cations using an ICP-SIFT tandem mass
spectrometer. It was found that CH3F mainly reacts in 5 ways, listed below.[38]
Page 4 of 65
M+ +CH3F
→ M+CH3F
(1) - Molecular addition
→ MF+ + CH3
(2) - F atom transfer
→ MCH2+ + HF
(3) - HF elimination
→MCHF+ + H2
(4) - Dehydrogenation
→ CH2F++ MH
(5) - Hydride transfer
In this project, the capabilities of the reaction gas CH3F to resolve the spectral overlaps that As and
Se suffer from was investigated. The main reaction path between the reaction gas and the elements
of interest was determined and a selective and sensitive method for As and for Se determination was
developed. These methods were evaluated in terms of sensitivity and limit of detection, and
compared to other modes of operation using no gas, He and single quadrupole mode and other types
of instrumentation, such as SF-ICP-MS. Additionally, validation was performed by use of simulated
matrices and by measurement of a diversity of certified reference materials.
Page 5 of 65
2. Theory
In this part, the theory behind the instrumentation and contamination will be discussed. Firstly, a
general description of the technique inductively coupled plasma-mass spectrometry (ICP-MS) will
be given, including its advantages and disadvantages. Subsequently a more detailed description of
the tandem mass spectrometer will be described and finally, the issues of contamination will be
discussed.
2.1 Instrumentation
2.1.1 ICP-MS in general
(6)
Ion detector
(5)
ICP-MS is a mass spectrometric technique,
which can be used to identify and quantify
(4)
(3)
Interface
Ion optics
(2)
Spray
chamber
Mass separation
device
Nebulizer
trace elements in samples. The advantages of
ICP-MS are its speed of analysis (high sample
throughput), low detection limits, and its
(1)
ICP Torch
Turbo
molecular
pump
Turbo
molecular
pump
Mechanical
pump
RF power
supply
isotopic and multi-element capabilities. In an
ICP-MS instrument, ions are formed in an
inductively coupled plasma and these ions are
then analyzed using MS. Figure 1 shows a
Figure 1 Schematic overview of an ICP-MS instrument: (1) Sample
introduction system, (2) ICP torch, (3) Interface region, (4) Ionfocusing system, (5) Mass separation device and (6) Ion detector.
[39]
Modification of figure from .
schematic overview of a basic ICP-MS instrument, starting with a sample introduction system (1),
comprising of a nebulizer and a spray chamber, followed by an ICP torch (2). Hereafter there is an
interface region (3) with the sampling and the skimmer cone, which is followed by an ion-focusing
system (4). After this, there is a mass separation device (5) and finally, there is an ion detector (6).
Region 1 and 2 are under atmospheric pressure, whereas 3 - 6 are kept under vacuum.[39]
2.1.1.1 Sample introduction system
The purpose of the sample introduction system ((1) on figure 1) is, as the name suggests, to
introduce a representative part of the sample into the system. For liquid samples, this can be split
into two events - aerosol formation and droplet selection. A liquid sample is transported to the
nebulizer using a peristaltic pump or by spontaneous nebulization due to a pressure drop in the
nebulizer, created by leading the nebulizer gas flow through a narrow hole at the tip of the
nebulizer, which is also known as the venturi effect. When the sample reaches the nebulizer,
Page 6 of 65
pneumatic action of the gas flow breaks the sample into a fine aerosol by mechanical force. The
typical gas used is argon. The nebulizer can have different designs, such as concentric,
microconcentric, microflow and cross-flow, where the choice of nebulizer can be done based on the
sample under investigation. In this project, the concentric nebulizer is used and a schematic
overview of the concentric nebulizer can be seen in figure 2, together with the aerosol
generation.[39]
6 mm Shell or barrel
Nozzle
Capillary
Seal
Radius
Shoulder
Capillary
Annulus
4 mm Uptake tube
(liquid input)
Sample
passage
Nozzle end
surface
Maria
Sidearm
(gas input)
A)
B)
Figure 2 A) Schematic overview of the concentric nebulizer and B) An aerosol generated by this nebulizer.[39]
This particular design of nebulizer gives good stability and sensitivity, particularly when analyzing
clean solutions, however, since the capillary is quite narrow, problems with blockage can be an
issue.[39]
After the nebulization process, the tiny droplets enter the spray chamber, where the droplet selection
takes place. Only the smallest droplets are sent off to the
Spray
chamber
Plasma torch
sample injector
Central
tube
plasma source for further analysis in order to limit the solvent
load of the plasma. Two typical designs are the Scott-type
double-pass and the cyclonic spray chamber, however only the
Scott-type double-pass spray chamber will be discussed here.
In the double-pass design (Figure 3) the aerosol from the
Drain
tube
Sample
aerosol
Figure 3 Schematic overview of the Scott[39]
type double-pass spray chamber.
nebulizer is guided into a central tube and the droplets then
pass through the entire length of the tube, where, due to
gravitational forces, the larger droplets (larger than ~ 10 μm in
diameter), will drop out and they are removed through a drain
tube, which is located at the end of the spray chamber. The smaller droplets (< 10 μm in diameter)
will however continue by passing between the central tube and the outer wall due to a positive
Page 7 of 65
pressure and from there, they go to the plasma source. This selection of only the smaller droplets
can however also be seen as a weak point of the instrumentation, since only 2 - 5 % of the sample is
introduced into the plasma source. A second feature of the spray chamber is to smoothen out the
nebulization pulses produced by the peristaltic pump if used. Furthermore, the spray chamber can
be externally cooled in order to reduce the introduction of solvent going to the plasma source,
which is often required when dealing with organic solvents.[39]
2.1.1.2 Plasma source and ion formation
There are different types of plasma sources, with inductively coupled plasma (ICP) being the most
common type of plasma source today, but other plasma sources exist, like the direct current plasma
(DCP) and the microwave-induced plasma (MIP). In this project, the ICP was used and thus, it is
the only one discussed.[39]
In the plasma source ((2) on figure 1), which consists of the plasma torch, an RF coil and a power
supply, the sample aerosol emerging from the sample introduction system is converted into ions. A
schematic overview of the ICP torch can be seen in figure 4. The plasma torch comprises of three
concentric tubes - an outer tube, a middle tube
and a sample injector. Between the outer and
Load coil
Plasma gas
or cool gas
middle tube the gas, which is used as plasma
and cool gas, flows, whereas the gas that flows
between the middle tube and the sample
Carrier gas with
injector, known as the auxiliary gas, is used to sample aerosol
optimize the position of the plasma. Finally, a
third gas, known as the nebulizer/carrier gas,
transports
the
sample
from
the
sample
Torch
Electrons
Time-dependent
ICP
moving along
magnetic field
circular paths
introduction system to the torch, where the gas
flow physically makes a hole in the ICP.[39,40]
[40]
Figure 4 Schematic overview of the ICP Torch.
However, before ionization of the sample can occur, the inductively coupled plasma has to be
formed. This is done by a load coil to which an RF power is applied, which results in an alternating
current that oscillates within the coil at a frequency of either 27.12 or 40.68 MHz. This generates a
strong time-dependent electromagnetic field in the top part of the torch, and by means of a high-
Page 8 of 65
voltage spark to the plasma gas flowing through the torch, some electrons are removed from their
argon atoms. These electrons, which are forced to move according to circular paths, lead to a
spiraling motion. This motion causes the electrons to have high energy and upon collision with
other argon atoms, these can be ionized: Ar + e- → Ar+ + 2e-, resulting in the removal of more
electrons. This results in a collision-induced ionization of argon, which will continue in a chain
reaction. As a result, a gas comprised of argon atoms, argon ions and electrons is obtained, which is
also known as an inductively coupled plasma. Additionally, the coil used in ICP-MS is grounded
so that the ICP potential remains close to zero, in order to avoid the formation of a secondary
discharge between the plasma and the grounded interface cone.[39,40]
A)
6500 K 7500 K 8000 K Preheating
zone
6000 K
Normal
analytical
zone
10,000 K
B)
Ions
Atoms Gas
Solid Liquid
Initial
radiation
zone
Ionization
Atomization
Vapirization
Drying
Figure 5 A) The different temperature zones in the plasma, and B) The transformation the sample undergoes in the plasma
from liquid to ions.[39]
Ion formation in the ICP-MS can be expressed as the generation of positively charged ions using a
high temperature plasma discharge. In the plasma, where different heating zones are present, as
shown in figure 5A, the sample undergoes a transformation from a liquid aerosol to ions, as shown
in figure 5B. First, the droplet is dried, forming a solid particle, the solid then transforms into gas
form due to vaporization and continues to a ground-state atom due to atomization. Finally, it
reaches the analytical zone of the plasma, where the temperature is 6000-7000 K, where, due to
collisions with energetic electrons, excited Ar atoms or Ar ions, the atoms are converted into ions.
The extent of positive ion formation is dependent on the ionization potential (IP) of the element and
the lower the IP, the easier it is to ionize the atom. After ionization, the ions continue to the
interface region. It should be mentioned that it is possible to work with different diameters of the
central tube of the torch and especially when using volatile organic solvents it is preferred to work
with smaller diameters to avoid extinguishing the plasma.[39]
Page 9 of 65
Sample
cone
Skimmer
cone
2.1.1.3 Interface region
Plasma
torch
The interface region ((3) in figure 1) bridges the pressure
difference between the plasma source (~ 1010 mbar) and the
mass spectrometer analysis region (10-6 mbar).[39]
Ion
optics
~2 Torr
vacuum
The interface comprises of 2 metallic cones (Figure 6) - the
RF coil
sampling cone has a central opening with a diameter of 0.8 1.2 mm, while the hole of the skimmer cone has a smaller
diameter of 0.4 - 0.8 mm. The region between the cones is
Figure 6 Schematic overview of the interface
[39]
region.
kept under a vacuum of 1 - 3 mbar and are conventionally made of nickel, but can also be made of
e.g., platinum, which is a lot more resistant to corrosive liquids.[39] After the ions are generated in
the plasma source, only a part of the ICP is guided into the interface region, where supersonic
expansion occurs between the sampling and skimmer cone due to a lower pressure, which results in
the composition of the plasma being frozen.[40] After this, the central beam departs through the
skimmer cone and is directed to the ion-focusing system.[39]
2.1.1.4 Ion-focusing system
As the ICP-MS is set up for detection of positive ions, an ion-focusing system ((4) in figure 1) is
needed for removal of neutral species, negative ions and electrons, and to focus the ion beam into
the mass analyzer. After the beam emerges from the
skimmer cone, the positively charged ion beam is
Ion flow
Ion
optics
Interface
generated, however, due to the net charge being
positive, the ions now repel each other and the center
of the beam will mainly consist of ions with high massto-charge ratio (m/z-ratio), whereas ions of low m/zratio will be driven to the outside. The degree to which
this occurs will depend on the kinetic energy of the
ions, where transmittance decreases with decreasing
kinetic energy. This is known as the phenomenon of
space-charge effect (Figure 7).[39]
Page 10 of 65
Heavy
mass ions
Medium
mass ions
Light
mass ions
Figure 7 Illustration of the space-charge effect produced due to
[39]
repulsion between ions.
In order to hold/bringback the ions in/to the center of the ion beam, ion optics are used, which are a
combination of one or more ion lenses to which a voltage is applied and this region is normally kept
under a vacuum of 10-3 mbar. The lens(es) only select(s) the positive ions, whereas neutral species,
electrons and negative ions are avoided using a physical barrier. Generally, three approaches can be
used as barrier: 1) Photon stop, where a metal disk is placed after the skimmer cone and all species
that do not change trajectory due to influence of electrostatics hit the disk, 2) Off-axis detector, and
3) Ion mirror, where the ion beam is bended over 90° into the mass analyzer using electrostatics.[39]
2.1.1.5 Mass analyzers
From the ion-focusing system, the ion beam enters the mass analyzer and the purpose of the mass
analyzer ((5) in figure 1) is to separate the ions as a function of their m/z-ratio and thereby
separating the ions, which are significant for the analysis, from everything else, such as the ions
derived from the matrix, other elements, the solvent etc.. This can be achieved using different types
of mass spectrometers, such as quadrupole mass filter, double-focusing sector field or a time-offlight mass spectrometer. The different devices have different advantages and disadvantages
concerning mass resolution, speed and cost, and the device used should be chosen on the basis of
the problem under investigation. The mass analyzer is kept under a vacuum of 10-6 mbar and it is
positioned between the ion-focusing system and the detector.[39]
Quadrupole mass filter
When using a quadrupole mass filter, separation is done using four rods (Figure 8), where on each
pair of rods a direct current (DC) component , +U or -U and a radio frequency (AC) component is
placed with the two pairs of rods
to
detector
quadrupole rods
having a DC component with opposite
sign and an AC component with a
phase difference of 180°.[40]
This results in a band pass filter,
exit slit
ions
stable path
where only ions of selected m/z-ratio
are allowed to pass through the set-up
to the detector. This is due to the
entrance slit
unstable path
Figure 8 Illustration of the basic principle of the quadrupole mass filter as mass
[40]
analyzer.
electrostatics steering the ions on a
trajectory that leads them all the way through, while ions of other m/z-ratios will collide with the
Page 11 of 65
rods. By changing the voltages applied to the quadrupole rods, different m/z-ratios can be
monitored and a scan of masses from 0 - 300 amu can be obtained.[39] The advantages of this
technique are its simplicity, the lower purchase price, its high scanning speed and its lower
sensitivity to differences in kinetic energy of the ions that enter the mass analyzer. However a
drawback of this technique is its unit mass resolution.[40]
Double-focusing sector field
This mass spectrometer comprises of two analyzers: an electromagnetic and an electrostatic
analyzer (ESA) and the way of combining both sectors leads to different set-ups: a standard (ESA
first) or a reverse Nier-Johnson geometry (ESA last) or a Mattauch-Herzog set-up. Figure 9 shows
an example of a set-up, in this case a reverse Nier-Johnson geometry. In the magnetic sector, the
ions are separated as a function of
their m/z-ratio, and the electrical
Magnetic
sector
sector focuses the ions on the basis
Electrostatic
sector
of their kinetic energy. The double
focusing
effect
refers
to
both
focusing of the energy and of the
direction, which means that ions of
Ion
acceleration
same m/z-ratio, but a difference in
kinetic energy and/or direction are
Ion source
focused in one point.[39,40] The main
Detector
Figure 9 Schematic overview of a reverse Nier-Johnson geometry for double[40]
focusing sector field.
advantage of this set-up is its high
mass resolution of Rmax ≈10.000,
while the scanning speed is still relatively high, although it takes a bit longer to generate a full mass
spectrum than when using a quadrupole mass filter and high costs are involved. Another
disadvantage is that you lose sensitivity by increasing the resolution, which amounts to a factor of
10 per resolution mode.[40]
+V
+V
Acceleration
Time-of-flight
In the time-of-flight (TOF) mass
Repeller
Flight tube
spectrometer, ions, in packages, are
accelerated over a difference in
Extraction region
potential and enter a flight tube,
ICP
Sampling cone & skimmer
[40]
Page 12 of 65
Figure 10 Schematic representation of the time-of-flight mass analyzer.
where the distance traveled is proportional to the mass and the amount of kinetic energy. By using a
reflectron, where ions with higher kinetic energy go in deeper, the ions with the same m/z-ratio are
focused in the same point even if they have a different kinetic energy. Figure 10 shows a schematic
representation of the TOF. With the TOF, unit mass resolution can be obtained, but the speed of
analysis is very fast and a full mass spectrum can be measured in only 0.033 ms.[39,40]
2.1.1.6 Ion detectors
After the mass analyzer, the ions reach the ion detector, which transforms the incident ions into
electrical pulses. The pulses are counted and the number of the pulses is proportional to the amount
of analyte ions, which is present in the sample. Different types of detectors can be used, such as
electron multipliers - continuous or discrete dynode - and faraday cups. Here only the discrete
dynode electron multiplier will be discussed.[39]
Signal out
6
(X10 )
In the discrete dynode electron multiplier (Figure
+ 2 KV
11), the ion hits the inner surface and an electron
is released. A potential difference is present
Ions in
between two subsequent dynodes, which leads to
the acceleration of the electrons towards the end of
the dynode and as the electron collides with the
inner surface, additional electrons are produced,
Figure 11 Schematic overview of the electron multiplier with
[40]
discrete dynodes.
leading to a multiplication effect of the electrons. Thus one ion reaching the detector leads to 107108 electrons. It is possible to use the detector in both pulse and analog mode in order to allow
determination of both low and high concentrations in the same sample. Due to the fact that
detection of one ion takes time and during this time no other ions can be detected, a phenomenon
called detection deadtime, τ, occurs and it is normally in the range of 5 - 100 ns. However, when the
value of τ is known, the software can automatically correct for this.[39,40]
2.1.2 Interferences in ICP-MS
The interference in ICP-MS can be split into two different categories - physical and chemical
interferences, which is due to volatility, viscosity, surface tension, density and/or sample transport;
and spectral and non-spectral interferences.[39]
Page 13 of 65
Spectral interference arises when two or more ions have the same or very similar m/z-ratio. The
interference can be in the form of an isobaric overlap, e.g.,
40
Ar+ /
40
Ca+, polyatomic ions
comprising of elements from the plasma gas, matrix, solvent or air, leading to argon-containing
polyatomic ions, e.g.,
153
40
ArC+ /
52
Cr+, oxide and hydroxide ions, e.g.,
32 16
S O+ /
48
Ti+,
136
Ba16O1H+ /
Eu+, or other types, e.g., 28Si35Cl+ / 63Cu+, or from doubly charged ions, e.g., 48Ca2+ / 24Mg+. The
degree of interference will depend on both the concentration of the interfering element and the
analyte element affected by the interference. Some spectral overlaps can be overcome or avoided by
using an appropriate procedure for digestion of the samples, aerosol desolvation, by separating the
element from the matrix before analysis, by using another sample introduction system, by using
mathematical interference correction equations or by using cool/cold plasma technology. Another
mean of overcoming spectral overlap is using a mass analyzer with a higher mass resolution than
just unit mass resolution, but this also involves higher costs. Alternatively one can also use a
collision/reaction cell, where a collision or reaction gas is used to overcome the interference. The
principles of the collision/reaction cell will be described in more detail in section 2.1.3.[39,40]
Furthermore, non-spectral interferences, whereby the matrix induces a signal suppression and/or
enhancement, can be compensated for by using sample dilution, internal standardization, standard
addition or a combination of these or isotope dilution. With regard to internal standardization, it is
important to choose an internal standard that is not present in the sample already and one that is
close to the analyte of interest both in mass number and in ionization potential in order to obtain a
good correction. Additionally, the internal standard is also used to correct for instrumental
instability and/or signal drift.[41]
2.1.3 Triple quadrupole mass spectrometry (ICP-MS/MS)
Typically quadrupoles as mass analyzers are not very good when it comes to dealing with spectral
interferences, since they only offer unit mass resolution. That is why nowadays a collision/reaction
cell is often placed in front of the quadrupole mass spectrometer, to deal with interferences on the
basis of chemical resolution.[39]
In the field of ICP-MS collision/reaction cell technology has proven to be a useful technique to
remove or avoid spectral interferences by either collision or reaction of the analyte and/or
interfering ions with a gas. The basic principle of a collision/reaction cell is that in a cell, which is a
Page 14 of 65
multipole - quadrupole, hexapole or octapole -, a collision/reaction gas is added. Typically the gases
used are He as collision gas and H2, O2, NH3 or CH4 as reaction gases. Depending on the ions
involved, the gas will either act as a collision gas or as a reaction gas, resulting in processes such as
transfer of a proton, transfer of a hydrogen atom, molecular association reactions, fragmentation due
to collision, loss in kinetic energy due to collision and focusing due to collision. By choosing the
gas wisely, it is possible to remove most spectral interferences. In case a chemical reaction is
exploited, either the interfering ions, whereby harmless non-interfering ions are produced, or the
analyte ions, in order to convert them to other ions, which can be determined interference-free at
another m/z-ratio, can be involved in reaction. After the collision/reaction cell, the ions continue to
a quadrupole mass analyzer, which separates the ions according to their m/z-ratio. However, it is
important to mention, that along with the reaction of interest, other undesirable collisions/reactions
take place, leading to the production of unwanted interfering ions. These can be discarded by either
discrimination based on kinetic energy or by discrimination based on mass.[39]
Discrimination by kinetic energy (Figure
Quadrupole
Cell
Pre-cell
12) has the purpose of discriminating
between unwanted product ions and the
analyte ions on the basis of their kinetic
From plasma
To detector
energy. This can be done by positioning a
potential barrier at the end of the collision
cell, whereby ions with less energy than
the potential of the barrier will not be able
to pass. In this way, the reaction product
ions, which have a lower kinetic energy,
Energy
barrier
Collision/reaction gas atom or
molecule
Analyte Ion M+ - small collision
cross-section
Polyatomic species e.g., ArX+ large collision cross-section
Figure 12 Overview of the principles behind kinetic energy discrimination.
will not be able to cross the energy barrier, while the more energetic analyte ions will be transmitted
to the mass spectrometer. Kinetic energy discrimination can be also be used to discriminate against
polyatomic ions. In this case, typically non-reactive gases are used, such as He or Xe. Polyatomic
ions are larger, collide more, loose more energy and can thus be prevented from entering the mass
spectrometer.[39,42]
Discrimination by mass has the purpose of discriminating against products produced via unwanted
reactions on the basis of their mass. For this purpose, the quadrupole offers better capabilities then
the higher order multipoles, due to less diffuse stability boundaries, whereby it is possible to
Page 15 of 65
[39]
selectively filter masses out. As a result, very reactive gases, such as H2, O2, CH4 or NH3, can be
added in the cell. This is beneficial since these gases tend to be better at reducing some inferences,
owing to more ion-molecule reactions occurring. Meanwhile, most of the reaction by-products that
could lead to new interfering ions are discarded in the quadrupole by the bandpass filter. This is
known as dynamic reaction cell technology.[39,43]
Sampling cone
Detector
Ion lens
Tandem mass spectrometry, in the form of
Q-pole (Q1)
Q-pole (Q2)
ICP-MS/MS, takes the concept of the
collision/reaction cell a step further. In the
MS/MS set-up (Figure 13), the mass
analyzer consists of a quadrupole (Q1)
followed by a collision/reaction cell, which
Plasma
Skimmer cone
Octopole reaction system
Figure 13 Schematic overview of the MS/MS set-up in relation to the
[44]
other compartments of the ICP-MS.
typically is a multipole - in the case of the Agilent 8800 ICP-QQQ it is an octopole, followed by a
second quadrupole (Q2). The purpose of the first quadrupole is to operate as a mass filter, and only
let the target analyte mass through, thereby preventing all off-mass ions from entering the cel1. This
results in a more efficient removal of interferences due to less unwanted species being present in the
cell. The cell can function both in a collision and in a reaction mode, as described above, depending
on the choice of gas and instrumental settings. Q2 then functions as a second mass filter and can
either be used in on-mass mode, where the unreactive analyte can be measured at its original mass,
which is now interference-free due to the reaction of the interfering ions in the cell with the reaction
gas, or in mass-shift mode, where the analyte, as a result of reactions with the reaction gas, has
moved to a new mass, where interference-free determination is possible. Additionally, the ICPMS/MS can be operated in both single quadrupole (SQ) mode and in MS/MS mode, where single
quadrupole mode refers to an instrumental setting of the instrument, where only the
collision/reaction cell and the second quadrupole, Q2, are used, and the bandpass of Q1 is operating
in "fully open" mass width. The MS/MS mode refers to the instrumental setting of the instrument
where both quadrupoles, Q1 and Q2 are used as mass filters.[22,35]
Page 16 of 65
42
42
48
+
Ca/ Ti
36 12 +
Ar C
33 + 34 +
S/ S
16 +
O2
32 +
S
48
+
Ca/ Ti
12 +
Ar C
33 + 34 +
S/ S
36
O2 Reaction gas
16
+
O2
32 16
S O
1st Quad (Q1)
Rejects ALL masses except
analyte (32S) and on-mass
interferences (16O2)
ORS3Cell
Converts S+ to SO+
product ion
+
2nd Quad (Q2)
Set at Q1 + 16 amu
Rejects all cell formed
ions apart from 32S16O+
Figure 14 shows a schematic representation of the ICP-MS/MS system functioning in the MS/MS mode for measuring
mass-shift mode in the form of 32S16O+.[22]
Figure 14 shows an example of MS/MS being used in mass-shift mode in order to measure
32
32
S in
S in
the form of 32S16O+. Here, Q1 is set at an m/z-ratio of 32, so only species with an m/z-ratio of 32 are
transmitted to the cell. In the reaction cell, the reaction gas O2 is used to convert 32S+ into 32S16O+. If
only 32S+ reacts with O2 in the reaction cell, 32S16O+ will be the only ion transmitted to the detector
when Q2 is set at an m/z-ratio of 48. The other species will be rejected since they are off-mass.[22]
Additionally, different scan modes are possible in the MS/MS mode, which can be used for research
and method development, such as product ion scan, neutral gain/loss scan and precursor ion scan. In
a product ion scan, the m/z-ratio is fixed via Q1 and with Q2, the full mass range is scanned. This
mode offers the possibility to evaluate if the analyte reacts or not, and if it reacts, to identify which
reaction product ion is the most abundant one, thereby aiding in the interpretation of what reactions
are taking place in the reaction cell. In a neutral gain/loss scan, Q1 and Q2 scan over the mass range
with a fixed mass difference. This mode can be used to only observe one transition, e.g., a fixed
mass difference of 16, which is the addition of an oxygen atom, and the original isotopic pattern can
be preserved while eliminating all other oxygen isotopes. In a precursor ion scan, the mass range is
scanned using Q1 and the Q2 m/z-ratio is fixed. This mode can be used for identifying the origin of
a reaction product determined at a specific m/z-ratio.[22,42,45]
The MS/MS set-up described here offers multiple advantages over the single quadrupole set-up
(SQ), which was the predecessor. The SQ only consists of the collision/reaction cell followed by a
quadrupole. Thus due to not having a quadrupole before the cell, all ions present in the ion beam
enter the cell and an ion, that was not leading to spectral overlap with the analyte before, can now,
due to reaction with the gas, become a new interference for the non-reactive analyte ion. This is
avoided in the MS/MS set-up by Q1, which rejects the parent ion and thereby does not let it reach
Page 17 of 65
the cell, and no new interference is formed. Additionally, in the SQ configuration, the mass-shift
method does not work if there are unreactive ions present originally at the new mass of the analyte
after reaction. Again this is not a problem in the MS/MS set-up, since these ions are rejected via Q1.
Thus, the ICP-MS/MS offers a large improvement in the performance of the reaction mode, and an
improvement is also seen in the collision mode, where the removal of interferences is also improved
due to the cell conditions remaining consistent even if the sample matrix varies.[22,45]
2.2 Contamination
In any analysis, it is important to keep contamination to a minimum, but especially when working
with trace elements (concentrations < 100 μg/g) and ultra-trace elements (concentrations < 0.001
μg/g), it is crucial to keep contamination to a minimum during sample preparation and analysis.[46]
This is due to the fact that any contamination can lead to a large contribution to the measured
concentration. However, by using a method blank, which contains all components except the
analyte and has been through all the same steps as the sample, it is possible to quantify the
contribution of contamination from reagents and the procedure used to prepare the sample in
general.[47] Additionally, reagents can also be chosen which have a high purity in order to minimize
the contamination, and the equipment used for sample preparation can also be carefully chosen.
This can be done by choosing materials that contain low levels of the elements of interest and
before use they can be pre-cleaned to remove additional contamination. Furthermore, working in a
clean environment can additionally reduce the amount or risk of contamination.[39]
Page 18 of 65
3. Experimental
3.1 Instrumentation
The instrument used in this work, to carry out all measurements, is an Agilent 8800 triple
quadrupole ICP-MS instrument (ICP-QQQ/Agilent technologies, Japan). The instrument is
equipped with an introduction system, comprising of a concentric nebulizer followed by a Scotttype double-pass spray chamber. This is then followed by an ICP torch with a central tube with an
inner diameter of 2.5 mm, the
sampling and the skimmer cone,
which are made from nickel, and the
mass
separation
device,
which
comprises of two quadrupole mass
analyzers
with
collision/reaction
an
octopole-based
cell
fitted
in-
between, and this is then followed by
the ion detector in the form of a
discrete dynode electron multiplier.
Figure 15 shows a picture of the
instrument used.
The instrument can be operated in the
Figure 15 Agilent 8800 ICP-QQQ, with zooms of the introduction system, the
octopole collision/ reaction cell and the electron multiplier. Modification of figure
[48]
from .
"vented mode" (no gas in the cell) or the cell can be pressurized with a collision gas (e.g., He) or a
reaction gas (e.g., H2, O2, NH3) or a mixture of both. However, in this project a rather
unconventional reaction gas was used, CH3F/He in a 10/90 % mixture, which further on will be
denoted CH3F. The gas was introduced via the 4th gas inlet, where the gas flow rate is controlled by
a mass flow controller (MFC), which is calibrated for O2, and allows a flow of 0 - 100 %, which is
equivalent to 0 - 1 mL/min O2. Another option would have been to attach the reaction gas to the 3rd
gas inlet, where higher flows are possible, but due the limitation of the set-up of the instrument, that
always mixes 1 mL/min He with the gas introduced via the 3rd gas inlet, this would not be
beneficial.
In this project, CH3F as a reaction gas in the collision/reaction cell, is evaluated for its possibilities
in interference-free determination of
75
As and of the Se - isotopes
77
Se, 78Se and
80
Se in different
types of simulated matrices and in certified reference materials, and the performance is compared to
Page 19 of 65
modes using He and no gas in the collision/reaction cell. Additionally, the performance of the
methods developed for the ICP-MS/MS are also compared with that of another type of
instrumentation, the Thermo Element XR sector-field ICP-MS instrument (Thermo Scientific,
Germany), which was - until now - the method of choice for the determination of low levels of As
and Se, since it offers the lowest detection limits. The most important instrument settings and
parameters used in the experiments in MS/MS mode and SQ mode for the Agilent 8800 ICP-QQQ
are listed in table 2 for As and Se and a full list of the instrument settings and parameters can be
found in appendix 1. Table 3 lists the conditions used for the Thermo element XR SF-ICP-MS
instrument.
Table 2 Instrument settings for the Agilent 8800 ICP-QQQ instrument when measuring As and Se.
Agilent 8800
Scan type
Analyte: As
No gas
He
CH3F
He
MS/MS or SQ
MS/MS
MS/MS
MS/MS or SQ
MS/MS
Low matrix
Plasma mode
Low matrix
1550 W
RF power
Carrier gas flow rate
Analyte: Se
CH3F
1.18 L/min
1550 W
1.18 L/min
1.05 L/min
1.13 L/min
72 %
-
4.0 mL/min He
100 %
Q1 Bias
-2.0 V
-1.0 V
0.0 V
-1.0 V
0.0 V
Octopole Bias
-4.1 V
-4.1 V
-18.0 V
-4.1 V
-18.0 V
Energy discrimination
-8.4 V
-8.4 V
5.0 V
-8.4 V
Reaction gas flow rate
-0.01
Q2 axis offset
-12.5 V
Q2 Bias
75 → 89
78 → 78
125 → 125
Q1→ Q2
Wait time offset
→ 89
→ 78
4 mL/min He
5.0 V
-0.01
-12.5 V
-13.0 V
75 → 75
78 → 78
75 → 75
78 → 78
2 ms
-12.5 V
77 → 91
→ 91
78 → 92
→ 92
80 → 94
→ 94
125 → 125 → 125
2 ms
Nr. Replicates
10
10
Nr. sweep replicates
100
100
Integration time
1s
1s
-13.0 V
77 → 77
78 → 78
80 → 80
125 → 125
Table 3 Instrument settings for the Thermo Element XR SF-ICP-MS instrument when measuring As and Se.
Scan type
Resolution
RF power
Carrier gas flow rate
Mass window
Search window
Integration window
Sample time
Sample/peak
Nuclides monitored
Total analysis time / sample
Page 20 of 65
Element XR
EScan
High
1200 W
0.975 L/min
100 %
70 %
60 %
0.01 s
20
75
As, 77Se, 78Se, 125Te
180 s
3.2 Samples and reagents
Reagents and solvents:
For sample preparation, high purity reagents were used. Water (H2O) was purified by a Direct Q-3
Milli-Q system (Millipore, USA) and HNO3 (14 M, pro analysis, Chemlab, Belgium) was prepared
from pro-analysis grade nitric acid by purifying it using a Teflon® sub-boiling distillation set-up
(Cupola still, PicoTrace®). Other reagents and solvents used were MeOH (25 M, Chromasolv®,
Sigma Aldrich, Germany), H2O2 (9.8 M, Trace select, Fluka, Belgium) and HF (28 M, trace
analysis, Fisher Chemicals, Great Britain).
Elemental standard solutions:
Elemental standard solutions of 1 g/L of As, Te, Nd and Zr (PlasmaCal, SCP Science, Canada), 1
g/L of Ca, Y, Ge and Zn (Inorganic Ventures, The Netherlands), 1 g/L of Mo, Gd and Sm (Alfa
Aesar, Germany), and 10 g/L of Se (Aldrich chemical company inc., USA) were used. From these
elemental standard solutions and from HCl (12 M, trace analysis, Chemlab, Belgium) standard
solutions used for optimization, internal standardization, calibration and simulated matrix
experiments were prepared by dilution with 0.14 M HNO3. Selenium and tellurium were used as
internal standards for measuring As and for the measurement of Se, only Te was used as internal
standard.
An external calibration curve was prepared by preparing a set of 5 standard solutions in the
concentration range 0 - 5 μg/L of As and of Se, respectively.
Samples:
The methods for the determination of As and of Se were validated using the certified reference
materials listed in table 4. These samples were analyzed following the procedure described under
sample preparation, section 3.3.
Page 21 of 65
Table 4 List of certified reference materials investigated along with their certified values for As and Se.
Certified value (μg/g)
As
Se
NBS SRM 1575 Pine needles
0.21 ± 0.04
NBS SRM 1573 Tomato leaves
0.27 ± 0.05
NIST SRM 1568a Rice flour
0.29 ± 0.03
0.38 ± 0.04
4.8 ± 0.3
CRM 526 Tuna fish tissue
NRC-CNRC DORM-4 Fish protein
6.80 ± 0.64
3.56 ± 0.34
BRC 414 Plankton
6.82 ± 0.28
1.75 ± 0.10
NBS SRM 1646 Estuarine sediment
11.6 ± 1.3
(0.6)a
NIST SRM 1566a Oyster tissue
14.0 ± 1.2
2.21 ± 0.24
NRC-CNRC TORT-3 Lobster Hepatopancreas
59.5 ± 3.8
10.9 ± 1.0
TM
Seronorm
a
b
79 ± 16
Trace elements Urine, Level 1, Sero, Norway
b
13.9 ± 2.8b
Non-certified concentration of constituent element
Unit of reference material, (μg/L), since it is not a solid
3.3 Sample preparation
3.3.1 Digestion procedure
Most of the certified reference materials measured during this study are solids, so in order to
analyze these, it is necessary to digest the material. This can be accomplished by using an
appropriate digestion procedure. A digestion can be performed in both closed and open vessels and
using different heat sources, such as microwave and hot plates. In this project, it was chosen to
conduct the digestion in a closed vessel due to the fact that As, in the form of AsH3, is volatile, and
to use a hot plate as heat source. The hot plate digestion was preferred over microwave digestion,
even though this often results in a longer digestion time. However, the hot plate digestions are
easier to perform, less prone to contamination and easier to control. For the development of the
digestion procedure, the literature was consulted and it was also taken into consideration that it
would not be advantageous to use HCl or HClO4 as oxidants, since the polyatomic ions
and
40
Ar37Cl+ interfere with the determination of
75
As and
40
Ar35Cl+
77
Se, respectively. The final digestion
procedure, which was followed, is given below. However, for samples comprising of sedimentary
material, this general digestion procedure was found not to be sufficient and to these samples, HF
was additionally added in order to also digest the silicates present in the material.
For the hot plate digestion, the certified reference materials were accurately weighed in a
Savillex®PFA vessel. Masses ranging between 0.0800 - 0.2200 g were used, to which 4 mL of 14
M HNO3 and 1 mL of 9.8 M H2O2 was added. In case of sediment, an additional 1 mL of 28 M HF
Page 22 of 65
was added to the material to fully digest the sample. The mineralization was carried out at 110 °C
overnight on a hot plate. Additionally, in each set of digestions, blanks were included. After
digestion, the digests were quantitatively transferred to centrifuge tube, and centrifuged for 5 min at
7000 rpm and 20 °C in order to precipitate any undigested solids and the samples were stored at 5
°C until analysis. For the determination of As, a 40-fold dilution with H2O was performed to reduce
the concentration of the concentrated acids added for the digestion and to reduce the matrix load.
For the analysis of Se, however, only a 20-fold dilution with H2O was performed, due to the fact
that the method for Se determination is less sensitive than the method for As determination and the
Se concentration in the reference materials were low. To all samples and standards, Te was added as
internal standard, with a final concentration of 5 μg/L and 10 μg/L for the determination of As and
Se, respectively. In order to avoid problems with the stability of the solutions and to reduce the risk
of contaminating the samples, all samples were measured within 24 h after sample preparation.
Additionally, before using of the Savillex®PFA vessels, these were cleaned using an extensive
procedure listed below in order to avoid possible contamination problems from previous digestions.
In step 1, the vessels were rinsed 3 times with H2O, whereafter they were left in a soap bath for 24
h. Hereafter, in step 2, the vessels were filled halfway with 7 M HNO3, which was prepared from 14
M HNO3 pro-analysis, and left for 24 h on a hotplate at 110 °C. Step 3 is the same as step 2, with
the addition of new 7 M HNO3. In Step 4, the vessels were filled with 6 M HCl, which was
prepared from 12 M HCl pro-analysis, and left for 24 h on a hotplate at 110 °C. Step 5 is the same
as step 4, with the addition of new 6 M HCl. In the final step the vessels were left open on a
hotplate, and they were removed as soon as they were completely dry. Between each step
mentioned above, the vessels were rinsed three times with H2O. The procedure was carried out
under clean lab conditions (class - 10).
3.3.2 Reconstitution procedure for urine
In order to analyze the freeze-dried SeronormTM reference material, the urine had to be reconstituted
prior to analysis. This was done following the procedure provided by the supplier, where firstly the
screw cap was removed and the septum was lifted until a groove was present so that air could enter
the vial. Secondly, after waiting 5 - 10 min, the septum was completely removed and 5 mL of H2O
was added to the vial containing the freeze-dried urine, whereafter the vial was closed completely
with the screw cap and left for 30 min. Finally, the material was quantitatively transferred to a
Page 23 of 65
Teflon Savillex®PFA vessel, in order to prevent contamination from the septum, screw cap and vial,
and stored at 5 °C until analysis. Prior to analysis, the resulting solution was diluted 20-fold with
0.14 M HNO3 in order to reduce the matrix load. To all samples and standards, Te was added as
internal standard, with a final concentration of 5 μg/L and 10 μg/L for the determination of As and
Se, respectively. In order to avoid problems with the stability of the solutions and to reduce the risk
of contaminating the samples, all samples were measured within 24 h after sample preparation.
Page 24 of 65
4. Results and discussion
Through the years, different approaches have been used using Q-ICP-MS equipped with a
collision/reaction cell for the determination of As and Se. These approaches often use more
conventional gases, such as He, H2, O2 and CH4, since these have proven to be useful, and the
prediction of the reaction path of the gases has been more or less straightforward, where e.g., O2 as
a gas in the reaction cell will often result in the atom transfer reaction, M+ + ½ O2 → MO+.[32]
However for more unconventional gases such as CH3F, the reaction gas which will be investigated
in this project, five main reaction paths exist, but higher order reaction products can also be formed.
Thus, it is difficult to predict the main reaction product. It is first with the introduction of ICPMS/MS that is has become relatively easy and straightforward to use such a gas, since the product
ion scan enables easy determination of the main reaction product(s) formed in the cell. In this work,
methods for the determination of As and Se using CH3F as a reaction gas have been developed and
compared with methods using the more conventional collision gas He and using no gas, by
comparing the approaches with regard to analytical performance and the ability to overcome
spectral interferences. Likewise, comparisons were also made with SF-ICP-MS. Further validation
of the methods using CH3F was performed by analyzing a set of various reference materials.
4.1 Optimization of ICP-MS/MS protocol for the determination of As and Se
4.1.1 As
For the interference-free determination of As, a method using CH3F as reaction gas in MS/MS
mode was developed and optimized and likewise, methods using no gas, He in MS/MS mode and
CH3F in SQ mode were also developed and optimized in order to compare the method using CH3F
as reaction gas, to these.
For all methods developed, the most important optimized settings and parameters are shown in table
2, section 3.1, whereas a full version is given in appendix 1.
4.1.1.1 CH3F
Starting from a standard method, it was possible to optimize the parameters to fit the problem in
question, which was the determination of As free of interference using CH3F as reaction gas in
MS/MS mode. Firstly it was necessary to identify which product ions were mainly formed. This
could be investigated in a fast and easy way by using a product ion scan, where the m/z-ratio of Q1
was set at the original analyte ion mass (75 amu), while Q2 scanned over the entire mass range, thus
from 0 - 260 amu. In order to be able to choose the product ion, which would give the overall
Page 25 of 65
highest signal intensity, four product ions scans were conducted using four different cell gas flow
rates, 25 %, 50 %, 75 % and 100 %, while measuring a 5 μg/L As standard solution in 0.14 M
HNO3. Figure 16 shows the results of these four scans, with signal intensities as a function of the
Q2 m/z-ratio, and the most important reaction products are indicated. The range shown is 0 - 150
amu, since above this, no more reaction products were present, at the CH3F flows used here.
Figure 16 Production ion scans for As, Q1: 75 and Q2: scanned, at different cell gas flow rates of CH3F as reaction gas for a
solution containing 5 μg/L As, where A: 25 %, B: 50 %, C: 75 %, and D: 100 % of the maximum flow rate. Range 10 - 150
amu.
It can be seen from figure 16 that as the cell gas flow rate increases, the spectra become more
complex due to the formation of more reaction products, especially in the upper end of the
spectrum, which is due to the formation of higher order complexes. In order to make it easier to
interpret the information from figure 16, figure 17 only displays the peaks with the highest
intensities, which can be used for the determination of As.
Page 26 of 65
+
AsCH2
100000
25%
50%
75%
100%
+
As
90000
70000
60000
50000
AsCH2(CH3F)
40000
+
CH2F
20000
C2H6F
+
CH3
+
AsF
AsCHF
75 →107
30000
+
+
75 → 94
Intensity (cps)
80000
+
+
AsF2
10000
75 →123
75 →113
75 → 89
75 → 75
75 → 49
75 → 33
75 → 15
0
Q1 → Q2 (amu)
Figure 17 Most important conversions in As - CH3F reactions at the four different flows investigated: 25, 50, 75 and 100 % of
the maximum flow rate.
Figure 17 shows the signal intensity at Q2 m/z-ratios of 15, 33, 49, 75, 89, 94, 107, 113 and 123. It
can be seen from the figure that at lower m/z-ratios (< 75 amu), charge-transfer product ions are
formed such as CH3+ (m/z-ratio = 15), CH2F+ (m/z-ratio = 33) and C2H6F+ (m/z-ratio = 49). At an
m/z-ratio = 75 unreacted As+ is present and it can be seen that as the cell gas flow rate of CH3F
increases, the signal intensity of As+ decreases. This is due to the presence of more gas in the cell,
which leads to more collisions and reactions. At higher m/z-ratios (> 75 amu) the product ions,
which are formed due to reaction with the analyte ion, can be seen such as AsCH2+( m/z-ratio = 89),
which is the result of HF elimination, AsF+ (m/z-ratio = 94), which is the result of F atom transfer,
AsCHF+(m/z-ratio = 107), which is the result of dehydrogenation, AsF2+ (m/z-ratio = 113), which
also is the result of F atom transfer and AsCH2+(CH3F) (m/z-ratio = 123), a higher order product,
which is the result of both HF elimination and molecular addition. The ion that shows the overall
highest signal intensity at a cell gas flow rate of 75 % is AsCH2+, and this is thus the main reaction
product formed when using CH3F. This coincides with literature, where it was likewise found that
the main product formed is AsCH2+ due to HF elimination.[38] Based on this observation, it was
chosen to use Q2 at mass 89 during all of the following measurements. Additionally, it can be seen
from the figure that the amount of the higher order product AsCH2+(CH3F) increases as the flow
rate goes up and if a higher concentration of CH3F in the reaction gas could be used, this might
become the main reaction product.
Page 27 of 65
After having identified the mass that will be selected via Q2, it was now possible to find the optimal
flow rate. This was done either manually by observing the signal intensity when changing the cell
gas flow rate between 0 - 100 % or by letting the software run a ramp cell gas scan, where a blank
solution, 0.14 M HNO3 and a 5 μg/L As standard solution were measured at different cell gas flow
rates. Figure 18 was obtained by using the setting Q1 = 75 amu → Q2 = 89 amu, where signal
intensity is shown as a function of cell gas flow rate, using an interval of 5 %.
120000
Intensity (cps)
100000
80000
75
AsCH2+
5 μg/L As
Blank (HNO
(HNO3,
3 0.14 M)
60000
40000
20000
0
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100
Cell gas flow rate (%)
Figure 18 Optimization of the CH3F reaction gas flow rate. Signal intensities are shown as a function of the cell gas flow rate
for a 0.14 M HNO3 blank solution (blue) and a 5 μg/L As standard solution (red).
It can be seen from figure 18 that the highest signal intensity is obtained for a cell gas flow rate of
70 %, thus the optimal cell gas flow is around a flow of 70 %. The final fine-tuning of the optimal
cell gas flow could be done manually, as described earlier, and it was found that at a flow of 72 %
the signal intensity was the highest and this was set as the optimal cell gas flow. Hereafter, it was
possible to fine-tune all the other parameters of the method in order to obtain the highest sensitivity.
This was done either manually and/or by using auto tune, where the software performs the
optimization of some of the parameters. This method is further on denoted as MS/MS-CH3F-As.
The method developed above was for MS/MS mode, using CH3F as reaction gas. Similarly it is
possible to develop a method for SQ mode, using CH3F as reaction gas. The only difference
between the two methods is the fact that in the SQ mode, Q1 is operated in "fully open" mass width.
Further on this method is denoted as SQ-CH3F-As.
Page 28 of 65
4.1.1.2 No gas
In order to assess the advantages of the MS/MS-CH3F-As method, a method was developed to
determine As using no gas in the cell in MS/MS mode. It is however expected that a method using
no gas will not be able to deal well with spectral overlap, due to the fact that no mechanism is
present to remove the on-mass interferences from, e.g.,
40
Ar35Cl+. A method was developed by
again starting from a standard method and optimizing the parameters in order to determine As using
no cell gas. Due to no gas being present in the collision/reaction cell, there was no need for the
identification of the main product ion, since the analyte ion to be measured will be 75As+, thus Q1
and Q2 were set at mass 75. Knowing this, it was possible to fine-tune all the parameters of the
method in order to obtain the highest signal intensity and thus the highest sensitivity. This could be
done either manually and/or by using auto tune, similar to the way the parameters were optimized
for the MS/MS-CH3F-As method. This method is further on denoted as MS/MS-no gas-As.
4.1.1.3 He
Furthermore, a method using He as collision gas in MS/MS mode was also developed and
optimized to evaluate the advantages of the MS/MS-CH3F-As method. The interference-free
determination of As using He as collision gas is based on the idea that it is possible to remove the
major on-mass polyatomic interference of
40
Ar35Cl+, owing to the fact that polyatomic ions are
larger and thus will collide more frequently with the He atoms and thus, lose their charge, dissociate
and/or lose a substantial amount of kinetic energy, enabling to discriminate against these ions.[39,49]
Starting from a standard method, it was possible to optimize the parameters in order to determine
As free of interference using He as collision gas. No product ion scan had to be performed, due to
the fact that He is a collision gas, thus the analyte ion will not engage in reaction forming a product
ion. However the cell gas flow of He had to be optimized, in order to find the flow, at which signal
intensity and thus, the sensitivity was highest, but also where the flow was high enough to eliminate
the polyatomic interference from
40
Ar35Cl+. This was investigated by measuring two standard
solutions, a 5 μg/L As standard solution in 0.14 M HNO3 and a 5 μg/L As standard solution with
1000 mg/L Cl in 0.14 M HNO3 interchangeably, at increasing flow rates of He and with Q1 and Q2
set at mass 75. The result can be seen in figure 19, where the signal intensity is shown as a function
of cell gas flow rate.
Page 29 of 65
80000
5 μg/L As
70000
5 μg/L As + 1000 mg/L Cl
Intensity (cps)
60000
50000
40000
30000
20000
10000
0
0.0
1.0
2.0
3.0
4.0
5.0
6.0
Cell gas flow rate (mL/min)
Figure 19 Optimization of the He collision gas flow rate. Signal intensities are shown as a function of the cell gas flow rate for
a 5 μg/L As standard solution (blue) and a 5 μg/L As standard solution with 1000 mg/L Cl (red).
From the figure, it can be seen that at a flow of 1.5 - 2.0 mL He/min the highest signal intensity is
obtained and at a flow of 3 mL He/min, the two lines coincide, indicating that a minimum flow of 3
mL He/min is needed in order to remove the polyatomic interference from 40Ar35Cl+. As one goes to
higher flow rates, the signal intensity decreases, thus it would be natural to choose a flow of 3 mL
He/min as the optimal flow. However, the recommendations from the company for the MS/MS
mode using He as collision gas, states that it is recommended to use a flow of 4 - 5 mL He/min.
Thus it was chosen to use a cell gas flow of 4 mL He/min even though this meant that a loss in
signal intensity would be obtained in comparison to using 3 mL He/min. After finding optimal flow
rate, all other parameters of the method could be fine-tuned to obtain the highest sensitivity. This
was done in a similar way to what was described for the MS/MS-CH3F-As method. This method is
further on denoted as MS/MS-He-As.
4.1.2 Se
As for As, a method to determine Se interference-free using CH3F as reaction gas in MS/MS was
developed and optimized. In this project the Se - isotopes 77Se, 78Se and 80Se were monitored, since
these isotopes are typically monitored in quadrupole ICP-MS, with
80
Se and
78
Se being the two
most abundant isotopes. Additionally a method, where more than one isotope could be determined,
was sought, since this opens up possibilities for isotopic analysis.
Page 30 of 65
Likewise a method in SQ mode using CH3F as reaction gas and a method using He as collision gas
in MS/MS mode were also developed and optimized in order to compare these with the method
using CH3F as reaction gas in the MS/MS mode. However no method using no gas was developed
for Se in order to protect the detector, due to the presence of
amounts, which interfere with the analyte ions
80
Se+ and
78
40
Ar40Ar+ and
40
Ar38Ar+ in large
Se+, respectively, and in the no gas
method no mechanism is present that can reduce these interferences.
For all methods developed, the most important optimized settings and parameters are shown in table
2, section 3.1, whereas a full version is given in appendix 1.
4.1.2.1 CH3F
As was the case for As, the starting point is again a standard method, that is optimized to fit the
problem in question, which is the interference-free determination of Se using reaction gas CH3F in
MS/MS mode. It was chosen to perform the development and optimization of the method for 80Se,
since it has the highest abundance of the Se - isotopes and it is also the most interfered isotope. As
for the method developed for As, it was firstly necessary to identify which product ions were
primarily formed. This was again done by performing a product ion scan, where the m/z-ratio of Q1
was set at a fixed value - the m/z-ratio of the original analyte ion (80 amu) - while Q2 scanned over
the entire mass range, thus from 0 - 260 amu. In order to choose the product ion with the overall
highest signal intensity, four product ions scans were conducted at the same flows of CH3F as used
for the method development for As and measuring a 5 μg/L Se standard solution in 0.14 M HNO3.
Figure 20 shows the results of these four scans, with signal intensities as a function of the Q2 m/zratio, and the most important reaction products are indicated. In the figure, only the range 10 - 120
amu is shown, because no reaction products are present above this m/z-ratio.
Page 31 of 65
Figure 20 Production ion scans for Se, Q1: 80 and Q2: scanned, at different cell gas flow rates of CH3F as reaction gas for a
solution containing 5 μg/L Se, where A: 25 %, B: 50 %, C: 75 %, and D: 100 % of the maximum flow rate. Range 10 - 120
amu.
It can be seen from figure 20 that as the cell gas flow rate increases, the spectra do not become more
complex as was seen for As, where more complex species could be seen at higher flow rates. This is
due to the absence of higher order complex formation for Se at the investigated CH3F flow rates. In
order to make it easier to interpret the information that can be obtained from figure 20, the peaks,
with the highest intensities that could be used for Se determination, are displayed in figure 21.
Page 32 of 65
+
CH2F
100000000
+
C2H6F
Se
10000000
Intensity (cps)
1000000
25%
50%
+
75%
+
CH3
100%
100000
+
SeCH2
10000
1000
100
10
80 → 94
80 → 80
80 → 49
80 → 33
80 → 15
1
Q1 → Q2 (amu)
Figure 21 Most important conversions in Se - CH3F reactions at the four different flows investigated: 25, 50, 75 and 100 % of
the maximum flow rate.
Figure 21 shows the signal intensity at Q2 m/z-ratios of 15, 33, 49, 80, and 94. From the figure, it
can be seen that at lower m/z-ratios (< 80 amu) charge-transfer product ions are formed, such as
CH3+ (m/z-ratio = 15), CH2F+ (m/z-ratio = 33) and C2H6F+ (m/z-ratio = 49). These product ions
were likewise observed for As. At an m/z-ratio = 80 unreacted Se+ is present and it can be seen that
as the cell gas flow rate of CH3F increases, the signal intensity of Se+ decreases due to more
collisions and reactions taking place. This trend was also observed for unreacted As. At higher m/zratios (> 80 amu) product ions, which are formed due to reaction with the analyte ion, can be seen,
such as SeCH2+ (m/z-ratio = 94), which is the result of HF elimination. The ion which shows the
overall highest signal intensity is CH2F+, however this ion is not appropriate to use for the
determination of Se, due to the fact that the amount of the product ion CH2F+ is not proportional to
the amount of Se present, since charge transfers can occur from all ions present in the reaction cell
and not just from 80Se+. The highest signal intensity, for ions which are not produced due to charge
transfer, is from the ion of the unreacted
80
Se+, but this ion is also not appropriate to use for the
determination of Se due to the fact that it suffers from interference from, e.g., 40Ar40Ar+. Thus, the
only suitable ion to use is the reaction product ion SeCH2+, and it can be seen that the signal
intensities of this ion increase as the flow goes up with a maximum signal intensity at a flow of 100
%. This type of reaction product ion - MCH2+ - was also observed for the reaction of As with CH3F,
which makes sense since As and Se are located next to each other in the periodic table and thus, it
Page 33 of 65
would be highly likely that these two would react in a similar way with CH3F. However, in
literature, it can be found that, as mentioned before, As is expected to form the reaction product
AsCH2+ upon reaction with CH3F in a reaction cell, whereas for Se the same paper states that no
reaction takes place between Se and CH3F.[38] This difference may be due to the use of a different
type of instrumentation and settings than that of the paper. However, in this work, SeCH2+ was
observed as a reaction product, and it was decided to use Q2 at a mass of 94 during all of the
following measurements of 80Se.
It is now possible to find the optimal cell gas flow rate, by either observing the signal intensity
while manually changing the cell gas flow rate between 0 - 100 % or, as was also done for As, the
software could perform a ramp cell gas scan, where a blank solution, 0.14 M HNO3 and a 5 μg/L Se
standard solution were measured at different cell gas flow rates. Figure 22 shows the result of the
ramp cell gas scan, where signal intensity is shown as a function of cell gas flow rate, using an
interval of 5 %.
12000
80
SeCH2+
Intensity (cps)
10000
8000
5 μg/L Se
(HNO3 0.14 M)
Blank (HNO3,
6000
4000
2000
0
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100
Cell gas flow rate (%)
Figure 22 Optimization of the CH3F reaction gas flow rate. Signal intensities are shown as a function of the cell gas flow rate
for a 0.14 M HNO3 blank solution (blue) and a 5 μg/L Se standard solution (red).
From figure 22, it can be seen that the highest signal intensity is obtained for a cell gas flow rate of
100 %, and this was set as the optimal cell gas flow. However, from looking at the curve of the 5
μg/L Se standard solution, it can be seen that at a flow of 100 %, the signal is at its maximum,
which may indicate that if a higher cell gas flow was possible by, e.g., using another CH3F/He
mixture or by attaching it to the 3rd gas inlet, where higher flow rates are possible, a higher signal
intensity and thus, a higher sensitivity might be obtained. However, due to the gas being attached to
Page 34 of 65
the 4th gas inlet, the maximum flow rate possible was 100 % (as mentioned in the experimental
section). Knowing the optimal cell gas flow, the other parameters of the method could be optimized
in order to obtain the highest sensitivity. This was done similar to the method for As, by observing
when a signal intensity increase was observed upon manually changing the settings and/or by using
auto tune. This method is further on denoted as MS/MS-CH3F-Se.
Furthermore, a method for SQ mode using CH3F as reaction gas was also developed in a similar
way as for As, where the SQ mode is similar to the MS/MS mode with the only difference being
that in SQ mode, Q1 operates in "fully open" mass width. This method is further on denoted as SQCH3F-Se.
4.1.2.2 He
To assess the advantages of the MS/MS-CH3F-Se method, a method using He as collision gas in
MS/MS mode was developed and optimized. As mentioned earlier, the three Se - isotopes 77Se, 78Se
and
80
Se, will be monitored, and for the development of the MS/MS-CH3F-Se method,
80
Se, the
isotope with the highest abundance, was used. However, for the development and optimization of
this method, it was chosen to use the isotope 77Se instead, since it is the only isotope that does not
suffer from ArAr+ interference (40Ar40Ar+ and
40
Ar38Ar+). Likewise, starting from a standard
method, it is possible to optimize the method to enable determination of Se using He as collision
gas. The idea behind the use of He as collision gas is similar to that described for As, and in order to
optimize the method, no product ion scan had to be performed, since He is only a collision gas.
However, the flow rate of He had to be optimized, in order to obtain the highest signal intensity and
thus, the highest sensitivity, as well as being able to eliminate polyatomic interferences effectively.
This was done by measuring a 5 μg/L Se standard solution and a blank solution, 0.14 M HNO3
interchangeably at increasing flows of He to observe when the major interference of
78
40
Ar38Ar+ on
Se+ was removed. In figure 23, the results are displayed, where signal intensity is shown as a
function of cell gas flow rate.
Page 35 of 65
40000
5 μg/L Se
35000
Blank (HNO
(HNO3,
3 0.14 M)
Intensity (cps)
30000
25000
20000
15000
10000
5000
0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
Cell flow gas rate (mL/min)
Figure 23 Optimization of He collision gas flow rate. Signal intensities are shown as a function of the cell gas flow rate for a 5
μg/L Se standard solution (red) and a 0.14 M HNO3 blank solution (blue).
It can be seen from figure 23 that, as the flow rate of He increases, the signal intensity of the blank
decreases, indicating that the interference from ArAr+ is reduced, but a decrease is also seen for the
Se standard, which is due to both a reduction of the ArAr+ interference and a reduction of the
transmission of the analyte ion Se+. At a flow of 4 mL He/min, the interference from
40
Ar38Ar+ is
removed, since the intensity of the blank signal is close to zero, and this was chosen as the optimal
He flow rate. The method was additionally optimized by fine-tuning all the other parameters of the
method, either manually and/or by using auto tune, similar to what was done for the Se using CH3F
as reaction gas. Further on this method is denoted as MS/MS-He-Se. However, this method was
only used to measure the isotopes
40
40
77
Se and
78
Se, since
80
Se suffers from a very pronounced
+
interference from Ar Ar and in order to protect the detector, it was chosen not to investigate if it
would be possible to monitor 80Se using He as collision gas.
4.2 Optimization of SF-ICP-MS protocol for the determination of As and Se
In order to further evaluate the MS/MS-CH3F-As and MS/MS-CH3F-Se methods, a method using a
different technique, SF-ICP-MS, was developed, since this is the typical technique used for
interference-free determination of As and Se nowadays. The polyatomic interferences from, e.g.,
40
Ar35Cl+ on
75
As+,
40
Ar37Cl+ on
77
Se+ and
40
Ar38Ar+ on
78
Se+ could be resolved using high
resolution. However the polyatomic interference from 40Ar40Ar+ on 80Se+ could not be overcome in
high resolution, since this requires a theoretical resolution of 9688[26], which is very close to the
Page 36 of 65
maximum resolution attainable with the SF-instrument, especially when taking into account that the
intensity of the 40Ar40Ar+ peak is a lot higher than that of the 80Se+ peak. Thus only 75As and the two
Se - isotopes
77
Se and
78
Se were monitored using SF-ICP-MS. The most important optimized
parameters and settings are shown in table 3, section 3.1.
4.3 Calibration data and limits of detection
4.3.1 As
The analytical performance of the method for interference-free determination of As using CH3F was
compared to the analytical performance of all the other methods developed. The sensitivity and
instrumental limits of detection and quantification of the methods developed along with other
parameters were assessed by measuring standard solutions of 0, 0.5, 1, 2.5 and 5 μg/L As in 0.14 M
HNO3. 10 consecutive replicate measurements were performed to determine the standard deviation
of the blank, the slope and the intercept. From the measurements, it was possible to calculate the
limit of detection (LOD) and limit of quantification (LOQ) as 3 and 10 times the standard deviation
on the blank divided by the slope, respectively.[47] In table 5, the results are presented for the various
ICP-QQQ methods, as well as for the Element XR SF-ICP-MS. The calibration curves can be seen
in appendix 2.
Table 5 Calibration data and instrumental LODs and LOQs obtained for As with ICP-MS/MS (several modes) and SF-ICPMS.
Set-up
mode
Reaction
gas
Q1
(amu)
Q2
(amu)
Sensitivitya
(L/μg)
Intercepta
(count s-1)
R2
LODb
(μg/L)
LOQb
(μg/L)
MS/MS
CH3F
75
89
18160 ± 250
-90 ± 100
0.999994
0.0005
0.002
MS/MS
No gas
75
75
28120 ± 73
133 ± 80
0.999992
0.0009
0.003
MS/MS
He
75
75
3914 ± 40
-11 ± 37
0.9999989
0.002
0.006
SQ
CH3F
-
89
34710 ± 580
-20 ± 170
0.999987
0.001
0.004
Nuclide monitored
75
As
824 ± 18
13 ± 12
0.99996
0.01
0.04
SF-ICP-MS
Uncertainties are expressed as standard deviation (n=10)
b
LOD and LOQ are calculated as 3 and 10 times the standard deviation of a blank solution (0.14 M HNO3) divided by the
slope of the calibration curve, respectively, using 10 consecutive replicate measurements of the blank to obtain the standard
deviation.
a
From table 5, it can be seen that the highest sensitivity is obtained with the SQ-CH3F-As method,
the second highest with MS/MS-no gas-As, followed by MS/MS-CH3F-As, while MS/MS-He-As is
the method, which shows the lowest sensitivity of the methods using the Agilent 8800 ICP-QQQ.
This complies with what is to be expected, since in SQ mode Q1 operates in fully open mode and
Page 37 of 65
As+ is more efficiently transported. Additionally, when comparing the sensitivities obtained in the
MS/MS mode, the MS/MS-no gas-As method has the highest sensitivity, which is also what would
be expected, since no gas is present in the cell with which As can collide or react with, losing its
positive charge or forming a reaction product. However, the sensitivity obtained with the MS/MSCH3F-As method is comparable to that obtained using no gas, indicating that the efficiency of the
reaction is high. Additionally, it can be seen that the lowest overall sensitivity was obtained using
the Element XR SF-ICP-MS, which is due to the use of the highest resolution setting, which
significantly reduces the sensitivity, but high resolution is necessary in order to resolve the
interference from, e.g.,
40
Ar35Cl, which requires a theoretical resolution of 7773.[26]
For all
calibration curves, a value of > 0.9999 was obtained for R2, which shows that the response is
proportional to the amount of analyte.
When comparing the instrumental LODs, it can be seen that the lowest LOD is obtained for the
MS/MS-CH3F-As method with 0.0005 μg/L, followed by MS/MS-no gas-As, SQ-CH3F-As and
MS/MS-He-As. However, it should be noted that these LODs do not give a good indication about
the real strength of the methods for dealing with spectral interferences, as they have been calculated
on the basis of measurements of pure standards and blanks. Therefore, the low LODs found for the
MS/MS-no gas-As and MS/MS-He-As methods can be misleading. In the MS/MS-no gas-As
method, no gas is present in the collision/reaction cell, which means that this method is not able to
cope with interferences, such as e.g.,
40
Ar35Cl+, which may be present when measuring a real
sample, and with the MS/MS-He-As method it is not possible to remove doubly charged interfering
ions, as will be demonstrated later on. The method with the highest LOD, is the Element XR SFICP-MS. In comparison to values that have previously been reported when measuring As, the
instrumental detection limit obtained with MS/MS-CH3F-As is definitely better than those obtained
using quadrupole ICP-MS (1.35 μg/L), where correction equations have also been used[19], doublefocusing sector field ICP-MS (0.004 μg /L)[33] and quadrupole-based ICP-MS equipped with a
collision/reaction cell using gases, such as H2/He (0.15 μg/L)[19] or other techniques such as atomic
absorption spectrometry (0.3 μg/L)[50]. Thus, this shows that with the MS/MS-CH3F-As method, it
is possible to obtain an instrumental LOD that is the lowest of what could be measured, but also of
what could be found in literature.
Page 38 of 65
4.3.2 Se
Also for Se, the analytical performance of the method using CH3F as reaction gas was compared to
that of all the other methods developed. Again sensitivity, instrumental limits of detection and
quantification and other parameters were assessed by measuring 10 consecutive replicate
measurements of standard solutions of 0, 0.5, 1, 2.5 and 5 μg/L Se in 0.14 M HNO3. Table 6 shows
the results obtained for the various ICP-QQQ methods, as well as for the Element XR SF-ICP-MS.
As for As, the calibration curves can be seen in appendix 2.
Table 6 Calibration data and instrumental LODs and LOQs obtained for Se with ICP-MS/MS (several modes) and SF-ICPMS.
MS/MS
Reaction
gas
CH3F
Q1
(amu)
77
Q2
(amu)
91
Sensitivitya
(L/μg)
286 ± 10
Intercepta
(count s-1)
3 ± 11
0.99998
LODb
(μg/L)
0.02
LOQb
(μg/L)
0.07
MS/MS
CH3F
78
92
917 ± 20
7 ± 13
0.999986
0.009
0.03
MS/MS
CH3F
80
94
1944 ± 25
-2 ± 22
0.99997
0.007
0.02
MS/MS
He
77
77
302 ± 8
0 ±13
0.99995
0.04
0.1
MS/MS
He
78
78
997 ± 22
99 ± 23
0.999991
0.06
0.2
SQ
CH3F
-
91
728 ± 26
3146 ± 72
0.9996
0.2
0.8
SQ
CH3F
-
92
1945 ± 20
317 ± 43
0.9997
0.02
0.06
SQ
CH3F
-
94
4075 ± 30
175 ± 33
0.99997
0.01
0.04
67 ± 5
2±5
0.9999
0.05
0.2
Set-up mode
R2
Nuclides monitored
SF-ICP-MS
77
Se
78
Se
223 ± 8
28 ± 17
0.9993
0.5
2
SF-ICP-MS
Uncertainties are expressed as standard deviation (n=10)
b
LOD and LOQ are calculated as 3 and 10 times the standard deviation of a blank solution (0.14 M HNO3) divided by the slope of
the calibration curve, respectively, using 10 consecutive replicate measurements of the blank to obtain the standard deviation.
a
It can be seen from table 6 that the highest sensitivity was obtained for the SQ-CH3F-Se method
followed by MS/MS-CH3F-Se, with which comparable sensitivities are obtained as with MS/MSHe-Se. As for As, the method with the lowest sensitivity is the Element XR SF-ICP-MS, which
again is due to the use of the highest resolution setting, which results in a reduction of sensitivity in
the order of 2 magnitudes, but again high resolution is necessary for the determination of Se, since
the interference from, e.g., 40Ar37Cl+ on 77Se+ requires a theoretical resolution of 9182 and 40Ar38Ar+
on 78Se+ requires a theoretical resolution of 9970.[26] Furthermore, it can be seen that the sensitivity
obtained for the MS/MS-CH3F-Se method is not very high in comparison to what was found for As,
since Se has multiple isotopes and the reaction to form SeCH2+ is less favorable. For all calibration
curves, a value above 0.999 was obtained for R2.
Page 39 of 65
From looking at the instrumental LODs that were obtained, it can be seen that the MS/MS-CH3F-Se
method has the lowest LOD of 0.007 μg/L via
78
80
Se, followed by
78
MS/MS-CH3F-Se via ( Se), SQ-CH3F-Se via ( Se and
78
Se. This is then followed by
80
Se), MS/MS-CH3F-Se via (77Se),
MS/MS-He-Se and SF-ICP-MS via (77Se), which all have comparable LODs. The highest LODs are
found for SQ-CH3F-Se via (77Se) and SF-ICP-MS via (78Se). However as for As, the LODs do not
give a good indication about the real strength of the methods for dealing with interferences, as the
method using He as collision gas, e.g., is unable to overcome doubly charged interferences, since
this method has no mechanism to remove these, as will be demonstrated later on. When comparing
the values obtained in this project with values reported in literature, it can be found that the
instrumental LOD obtained for MS/MS-CH3F-Se via
using Q-ICP-MS (0.28 μg/L via
82
80
Se is definitely better than those obtained
Se+ and by using correction equations)[19] and Q-ICP-MS
equipped with a collision/reaction cell using other gases than CH3F such as H2/He (0.029 μg/L via
80
Se+)[19], and comparable to those obtained using SF-ICP-MS (0.004 μg /L via 82Se+)[34]. Thus even
though the reaction of Se with CH3F is less favorable than that of As, low LODs are still found.
4.4 Investigation of the improvement in sensitivity by the addition of MeOH
4.4.1 As
As mentioned in the introduction, As and Se have high ionization potentials and thus are poorly
ionized and in literature, it can be found that carbon, e.g., in the form of MeOH[4,29,31], can be added
to induce the carbon effect and thereby increase the sensitivity for the analyte. With the increase in
sensitivity, it might also be possible to decrease the limit of detection and in ultra-trace level
determinations, it is the aim to be able to determine the analyte at as low concentrations as possible.
However, it also has to be mentioned that the addition of carbon can also be used to resolve the
problem of the carbon effect when standards and samples differ in matrix if it is not possible to find
an appropriate internal standard that experiences a similar enhancement as the analyte.
In order to investigate the increase in sensitivity for As, solutions containing 5 μg/L As standard
solution in HNO3/MeOH - 100/0 %, 98/2 %, 96/4%, 94/6%, 92/8%, 90/10 % and the corresponding
blank solutions were prepared and analyzed using the MS/MS-CH3F-As method. Figure 24 shows
the results, both as signal intensity and as ratio, calculated as signal 5 μg/L As / signal blank, as a
function of MeOH concentration.
Page 40 of 65
3000
200000
2500
5 μg/L As
150000
2000
Blank (HNO
(HNO3,
0.14M)
M)
3, 0.14
1500
Ratio
100000
Ratio
Intensity (cps)
250000
1000
50000
500
0
0
0
2
4
6
8
10
Conc. MeOH (%)
Figure 24 Investigation of the influence of the addition of MeOH. Signal intensity is shown as a function of MeOH
concentration for a blank solution, 0.14 M HNO3 with increasing MeOH concentration (blue), and a 5 μg/L As standard
solution 0.14 M HNO3 with increasing MeOH concentration (red). Additionally, the ratio is also shown as a function of
MeOH concentration, where the ratio (green) is calculated as signal 5 μg/L As / signal blank.
It can be seen from figure 24 that with 94/6 % HNO3/MeOH, the highest signal intensity is seen for
the 5 μg/L As standard solution and the signal intensity has doubled in comparison to no addition of
MeOH. However as the amount of MeOH goes up, the intensity for the blank also increases due to
the impurities in the MeOH and due to an increase in the sensitivity for the blank. When calculating
the ratio between the signal for the 5 μg/L As and the blank solution, a decreasing relationship is
observed (green ratio curve). Thus, even though the signal intensity for 5 μg/L As standard solution
is more than doubled when using 94/6 % HNO3/MeOH, the signal for the blank has increases even
more. Additionally, above 6 % MeOH, a signal decrease is observed for the 5 μg/L As standard
solution, which can be linked to a decrease in plasma efficiency, since the plasma was cooled down
by the introduction of MeOH.
In order to determine if addition of MeOH would be beneficial, the analytical performance was
assessed using a calibration curve prepared using 94/6 % HNO3/MeOH in the concentration range 0
- 5 μg/L of a As standard solution. The results are given in table 7, together with the results
obtained for a calibration curve prepared in pure HNO3. The calibration curve can be seen in
appendix 3.
Page 41 of 65
Table 7 Calibration data and instrumental LODs and LOQs obtained for As with ICP-MS/MS using MS/MS-CH3F-As and
HNO3 and HNO3/MeOH 94/6 % as solvent.
Set-up
mode
Reaction
gas
Q1
(amu)
Q2
(amu)
Solvent
Sensitivitya
(L/μg)
Intercepta
(count s-1)
R2
LODb
(μg/L)
LOQb
(μg/L)
MS/MS
CH3F
75
89
HNO3
18160 ± 250
-90 ± 100
0.999994
0.0005
0.002
MS/MS
CH3F
75
89
94/6 % HNO3/MeOH
45700 ± 1200
-700 ± 1700
0.9999
0.001
0.004
a
Uncertainties are expressed as standard deviations (n=10)
LOD and LOQ are calculated as 3 and 10 times the standard deviation of a blank solution (0.14 M HNO 3) divided by the slope of
the calibration curve, respectively, using 10 consecutive replicate measurements of the blank to obtain the standard deviation.
b
From table 7, it can be seen, that when using 94/6 % HNO3/MeOH as solvent, a sensitivity increase
is indeed observed, which coincides with what was seen in figure 24. However, when looking at the
instrumental LODs, it is seen that the LOD, for the method using 94/6 % HNO3/MeOH as solvent,
is higher than that with the method using no MeOH. Thus, it was decided not to use the addition of
MeOH further on in this project, since this study is aimed at determining As at ultra-trace levels and
for this purpose, an as low as possible LOD is preferred.
4.4.2 Se
Also for Se, it was investigated if it would be beneficial to add MeOH to the solvent by measuring
solutions containing 5 μg/L Se and blank solutions in HNO3 with 0 - 10 % MeOH using the
MS/MS-CH3F-Se method. Figure 25 shows the results, with both signal intensity and ratio, which is
30000
200
180
160
140
120
100
80
60
40
20
0
Intensity (cps)
25000
20000
5 μg/L Se
15000
Blank
Blank (HNO3,
(HNO3, 0.14 M)
10000
Ratio
5000
0
0
2
4
6
Conc. MeOH (%)
8
Ratio
calculated as signal 5 μg/L Se / signal blank, as a function of the MeOH concentration.
10
Figure 25 Investigation of the influence of the addition of MeOH. Signal intensity is shown as a function of MeOH
concentration for a blank solution, 0.14 M HNO3 with increasing MeOH concentration (blue), and a 5 μg/L Se standard
solution 0.14 M HNO3 with increasing MeOH concentration (red). Additionally, the ratio is also shown as a function of
MeOH concentration, where the ratio (green) is calculated as signal 5 μg/L Se / signal blank.
Page 42 of 65
From figure 25, it is seen that with 94/6 % HNO3/MeOH, the highest signal intensity is observed for
the 5 μg/L Se standard solution, with the signal intensity doubled in comparison to no addition of
MeOH. However, also here, the signal intensity of the blank increases with increasing MeOH
concentration, which again is due to the impurities present in the MeOH used and due to a
sensitivity increase for the blank as well. A decreasing relationship is observed (green ratio curve),
when the ratio between the signal for the 5 μg/L Se and the blank solution is calculated. Thus, the
signal for the blank has increased even more than the signal for 5 μg/L Se standard solution. As for
As, above 6 % MeOH, a signal decrease is observed for the 5 μg/L Se standard solution.
Similar to what was done for As, a calibration curve in the concentration range 0 - 5 μg/L Se
standard solution in 94/6 % HNO3/MeOH was measured to assess if the addition of MeOH would
be favorable. In table 8, the calibration data are given together with the results obtained for a
calibration curve prepared in pure HNO3 and the calibration curve can be seen in appendix 3.
Table 8 Calibration data and instrumental LODs and LOQs obtained for Se with ICP-MS/MS using MS/MS-CH3F-Se, and
HNO3 and HNO3/MeOH 94/6 % as solvent.
Set-up
mode
Reaction
gas
Q1
(amu)
Q2
(amu)
Solvent
Sensitivitya
(L/μg)
Intercepta
(count s-1)
R2
LODb
(μg/L)
LOQb
(μg/L)
MS/MS
CH3F
77
91
HNO3
286 ± 10
3 ± 11
0.99998
0.02
0.07
MS/MS
CH3F
78
92
HNO3
917 ± 20
7 ± 13
0.999986
0.009
0.03
MS/MS
CH3F
80
94
HNO3
1944 ± 25
-2 ± 22
0.99997
0.007
0.02
MS/MS
CH3F
77
91
94/6 % HNO3/MeOH
725 ± 12
38 ± 21
0.9999
0.02
0.07
MS/MS
CH3F
78
92
94/6 % HNO3/MeOH
2295 ± 41
128 ± 29
0.9999
0.02
0.06
80
94
94/6 % HNO3/MeOH
5042 ± 80
263 ± 42
0.9999
0.009
0.03
MS/MS
CH3F
Uncertainties are expressed as standard deviations (n=10)
b
LOD and LOQ are calculated as 3 and 10 times the standard deviation of a blank solution (0.14 M HNO 3) divided by the slope of
the calibration curve, respectively, using 10 consecutive replicate measurements of the blank to obtain the standard deviation.
a
It can be seen in table 8, that a sensitivity increase is observed for all isotopes when using 94/6 %
HNO3/MeOH as solvent, as expected from the results in figure 25. When looking at the limits of
detection obtained, it can however be seen that the LODs for the method using 94/6 %
HNO3/MeOH as solvent are comparable or slightly higher than those without MeOH. Thus, the
overall LOD is not better than what is obtained via the isotope
80
Se using no MeOH and
additionally, by adding MeOH the sample preparation also gets more complex. Thus, it was
decided, as for As, not to use the addition of MeOH further on in this project when measuring Se.
Page 43 of 65
4.5 Results obtained for simulated matrices
4.5.1 As
To further validate the method for determination of As using CH3F as reaction gas in MS/MS mode,
different simulated matrices were prepared and measured in order to demonstrate that with this
method, it is possible to remove interferences that often cause problems in the determination of As
using other methods, such as no gas and He in MS/MS mode and CH3F in SQ mode. This was done
by investigating the most important interferences that are present at mass 75, and thus could
interfere with the measurement of the analyte ion 75As+ and by investigating potential interferences
introduced, when a reaction product is measured instead of the original analyte ion, when using
CH3F as reaction gas. Table 9 lists the interferences investigated using simulated matrices.
Table 9 List of on-mass and mass-shift interferences investigated using simulated matrices for As.
Type of interference
75
+
On-mass interference of As
Mass-shift interference due to the use of CH3F as reaction gas forming the
reaction product AsCH2+
Mass (amu)
75
40
89
Interference
Ar Cl+, 150Nd2+, 150Sm2+
35
89
Y+, 70Ge19F+, 70Zn19F+
Simulated matrices containing 5 μg/L As standard solution with 500 mg/L Cl and with 100 μg/L Nd
and Sm were investigated in the MS/MS mode, using the gases CH3F and He, and using no gas.
Additionally, in the MS/MS mode and in the SQ mode using CH3F as reaction gas, the following
simulated matrices were investigated: 5 μg/L As standard solution with 1 μg/L Y, with 5 μg/L Ge
and with 10 μg/L Zn. The concentrations of the elements investigated here were chosen in such a
way that the concentration was high enough to observe the interference, but not more than this, in
order to minimize contamination of the system and to protect the detector. For comparison, a pure 5
μg/L As standard solution (no matrix elements added) was also measured in all modes. All samples
contained 10 μg/L Se, which was used as internal standard (using the isotope
78
Se+). When these
experiments were performed, in the early stages of the project, Se was selected as internal standard,
since it has a similar mass and ionization potential as As, and it was added to be able to correct for
signal suppression and/or enhancement. However, in experiments later on, Se has been replaced by
Te as internal standard, since Se was present in some of the reference materials investigated. Figure
26 shows the results obtained when measuring the simulated matrices in the different modes with
the different gases and by using external calibration. The red line indicates the concentration of 5
μg/L As, as present in all solutions.
Page 44 of 65
15.0
MS/MS, CH
CH3F
3F
MS/MS, no gas
12.5
MS/MS, He
(3)
[As] (μg/L)
10.0
7.5
(1)
(4)
(5)
SQ, CH
CH3F
33F
CH3F
(2)
(6)
5.0
2.5
0.0
5 μg/L As
5 μg/L As +
500 mg/L Cl
5 μg/L As +
100 μg/L
Nd/Sm
5 μg/L As +
1 μg/L Y
5 μg/L As +
5 μg/L Ge
5 μg/L As +
10 μg/L Zn
Figure 26 Simulated matrices. Concentration of As measured with MS/MS-CH3F-As (blue), with MS/MS-no gas-As (red),
with MS/MS-He-As (green) and with SQ-CH3F-As (purple) is plotted against the different simulated matrices. (n = 5)
It can be seen from figure 26 that in all modes, it was possible to obtain 5 μg/L As when no matrix
elements were present (1). However, in the case of the simulated matrix containing 5 μg/L As and
500 mg/L Cl (2), more than 5 μg/L As was found with the MS/MS-no gas-As method, which is due
to the method not being able to overcome the polyatomic interference from 40Ar35Cl+, which is also
present at mass 75. The other methods were able to overcome this interference and accurate results
were obtained. With the MS/MS-He-As method the interference was overcome due to collision of
the polyatomic interfering ion with the He atoms and subsequent kinetic energy discrimination,
while with the MS/MS-CH3F-As method, the interference was overcome by using the mass-shift
method, (Q2 = 89), where As was measured at mass 89 as AsCH2+.
In the case where the simulated matrix contains 5 μg/L As and 100 μg/L Nd and Sm (3), it was not
possible to obtain accurate results with both MS/MS-no gas-As and MS/MS-He-As. This is due to
both methods not being able to remove the doubly charged 150Nd2+ and 150Sm2+ ions, which appear
at the m/z-ratio 75. However, with the MS/MS-CH3F-As method accurate results were obtained by
again overcoming the interferences due to the mass-shift method (Q2 = 89), where As is measured
at mass 89 as AsCH2+, where there is no interference present from the doubly charged ions.
For the simulated matrices, which contain 5 μg/L As and 1 μg/L Y (4) and 5 μg/L Ge (5),
respectively, it can be seen that with the SQ-CH3F-As method more than 5 μg/L As was obtained.
This is due to the method not being able to remove the interference from
Page 45 of 65
89
Y+ and from
70
Ge19F+,
which was formed in the reaction cell by F atom transfer from the reaction gas CH3F, since these
ions overlap with the mass of the reaction product ion formed in the reaction cell, AsCH2+ (m/zratio = 89). The lack of removal of the interferences is due to the fact that in SQ mode there is no
barrier present before the reaction cell to hinder 89Y+and 70Ge+ from entering the cell. In the case of
the MS/MS-CH3F-As method, accurate results were obtained for both (4 and 5), which is due to the
fact, that in the MS/MS mode, the interfering ions
89
Y+ and
70
Ge are removed by Q1, (Q1 = 75),
which only lets ions through which are on-mass with the m/z-ratio 75.
Finally, for the simulated matrix containing 5 μg/L As and 10 μg/L Zn (6) both the SQ-CH3F-As
method and the MS/MS-CH3F-As method lead to accurate results. Thus, the reaction product ion
70
Zn19F+ is apparently not an interference for neither of the methods under the investigated
conditions, which can either be due to the fact that the reaction product ion is not formed in the
reaction cell or due to the use of a too low concentration of Zn in the experiment.
Thus, only when using MS/MS mode with CH3F as reaction gas, it was possible to obtain 5 μg/L As
for all simulated matrices. Thus, it was the only method, which could overcome all investigated
interferences. Figure 27 is a schematic representation, showing how the different interferences are
overcome with the MS/MS-CH3F-As method for the interference-free determination of
75
75
As as
AsCH2+.
Figure 27 Schematic representation of the operating principle of the Agilent 8800 instrument when using the MS/MS-CH3FAs method, leading to an interference-free determination of 75As as 75AsCH2+. Modification of figure from[35].
Page 46 of 65
4.5.2 Se
Also for Se, simulated matrices were investigated, to demonstrate that the MS/MS-CH3F-Se method
is able to overcome interferences that other methods, such as He and SQ mode using CH3F, fail to
overcome. As for As, this was done by investigating how the methods deal with the most important
interferences that are present at the original mass of the analyte and thus could interfere with the
measurement of
77
Se+, 78Se+ and
80
Se+ . However, it was not necessary to investigate the strongest
type of interference, 40Ar40Ar+ interfering with the determination of 80Se+ and 40Ar38Ar+ interfering
with the determination of 78Se+. This interference is always present due to the use of argon as carrier
gas and it was already investigated before during method development, where it was possible to
check in the blank if this interference was present. No additional interferences were investigated for
80
Se, since it was chosen not to monitor
80
Se in the He method and likewise, no studies of the
MS/MS mode using no gas was conducted to protect the detector, as mentioned before.
Additionally, potential interferences introduced, when a reaction product is measured at masses 91,
92 and 94 instead of the original ion mass when using CH3F as reaction gas, were also investigated.
Table 10 lists the interferences investigated using simulated matrices.
Table 10 List of on-mass and mass-shift interferences investigated using simulated matrices for Se.
Type of interference
Mass (amu)
Interference
Ar37Cl+, 40Ca37Cl+
40
77
154
Sm2+, 154Gd2+
On-mass interference
156
Gd2+
78
91
Zr+, 72Ge19F+
91
Mass-shift interference due to the use of CH3F as reaction gas
+
forming the product SeCH2
92
92
Zr+, 92Mo+, 73Ge19F+
94
94
Zr+, 94Mo+, 75As19F+
In the MS/MS mode, using the gases CH3F and He, the following simulated matrices were
investigated: 5 μg/L Se standard solution with 500 mg/L Cl, with 500 mg/L Cl and 100 μg/L Ca,
with 1 μg/L Sm and with 10 μg/L Gd. Additionally, simulated matrices containing 5 μg/L Se
standard solution with 5 μg/L Zr, with 0.1 μg/L Mo, with 0.1 μg/L Ge and with 10 μg/L As were
investigated in the MS/MS mode and in the SQ mode using CH3F as reaction gas. As for As, the
concentrations of the elements were selected such that the interference would be observed, but not
more than that. In order to demonstrate that it is possible to obtain accurate results for a pure Se
standard (no matrix), a 5 μg/L Se standard solution was also measured in all modes. All samples
contained 10 μg/L Te, which was used as internal standard (using the isotope 125Te). Tellurium was
selected as internal standard, since its mass is not too far from the masses of the Se - isotopes and it
Page 47 of 65
has a similar ionization potential, such that is can be used to correct for signal suppression and/or
enhancement. Figure 28 shows the results obtained when measuring the simulated matrices in the
different MS/MS modes and by using external calibration, whereas figure 29 shows the results
obtained when measuring the simulated matrices using CH3F as reaction gas, in the MS/MS mode
and in the SQ mode and by using external calibration. For each of the simulated matrices, only the
isotopes expected to suffer from interference, due to the presence of a particular element in the
sample, are shown. The red line indicates the expected concentration of Se at 5μg/L, as present in
all solutions.
15
[Se] (μg/L)
CH3F 77 → 91
CH3F,
CH3F,
CH3F 78 → 92
10
CH3F 80 → 94
CH3F,
(1)
(2)
(3)
(4)
(5)
He, 77 → 77
He, 78 → 78
5
0
5 μg/L Se
5 μg/L Se + 5 μg/L Se + 5 μg/L Se + 5 μg/L Se +
500 mg/L Cl 500 mg/L Cl 1 μg/L Sm 10 μg/L Gd
+ 100 μg/L
Ca
Figure 28 Simulated matrices. Se concentration measured with MS/MS-CH3F-Se, 77 → 91 (dark blue), 78 → 92 (red), 80 →
94 (green), and with MS/MS-He-As, 77 → 77 (purple), 78 → 78 (light blue) is plotted against the different simulated matrices.
(n = 5)
Figure 28 shows that for all MS/MS methods and for all isotopes, it was possible to obtain accurate
results for Se when no extra matrix elements were added (1). When the simulated matrix contained
5 μg/L Se and 500 mg/L Cl (2) and 500 mg/L Cl and 100 μg/L Ca (3), respectively, both methods
led to accurate results for Se. As was the case for As, the polyatomic interferences
40
Ca37Cl+ on
77
40
Ar37Cl+ and
Se+ were removed by energy loss through collision and subsequent kinetic energy
discrimination with the MS/MS-He-Se method, (77 → 77), and with the MS/MS-CH3F-Se method,
(77 → 91), the polyatomic interference could be overcome by using the mass-shift method, (Q2 =
91), where 77Se is measured at mass 91 as 77SeCH2+.
In the case where the simulated matrices contained 5 μg/L Se and 1 μg/L Sm (4) and 10 μg/L Gd
(5), respectively, it was seen that more than 5 μg/L Se was obtained using the MS/MS-He-Se
Page 48 of 65
method, (77 → 77) and (78 → 78). This is because the MS/MS-He-Se method, (77 → 77) is not
able to overcome the interference from the doubly charged interfering 154Sm2+ ion. The MS/MS-HeSe method, (77 → 77 and 78 → 78), is also not able to overcome the doubly charged interference
from 154,156Gd2+, where it can be seen that the interference is more obvious for the 78Se isotope than
for the
77
Se isotope, which is caused by the fact that
154
Gd (2.18 %) is less abundant than
156
Gd
(20.47 %). The same was seen for the As method using He as collision gas, where this method was
also not able to overcome the interference from the doubly charged ions. However with the
MS/MS-CH3F-Se method, (77 → 91, 78 → 92), 5 μg/L Se was again found for both (4 and 5),
which again is owing to the successful use of the mass-shift mode.
20
MS/MS, 77 → 91
MS/MS, 78 → 92
[Se] (μg/L)
15
(2)
(3)
(4)
MS/MS, 80 → 94
SQ,→ 91
10
SQ,→ 92
(1)
(5)
SQ,→ 94
5
0
5 μg/L Se
5 μg/L Se + 5 μg/L Se + 5 μg/L Se + 5 μg/L Se +
5μg/L Zr 0.1 μg/L Mo 0.1 μg/L Ge 10 μg/L As
Figure 29 Simulated matrices. Se concentration measured with MS/MS-CH3F-Se, 77 → 91 (dark blue), 78 → 92 (red), 80 →
94 (green), with SQ-CH3F-Se, → 91 (purple), → 92 (light blue), → 94 (orange) is plotted against the different simulated
matrices. (n = 5)
From figure 29, it can be seen than when no additional matrix elements were present (1), it was
possible to obtain 5 μg/L Se with all methods relying on CH3F as reaction gas in MS/MS and SQ
mode. However, in the case of the simulated matrix containing 5 μg/L Se and 5 μg/L Zr (2) and 0.1
μg/L Mo (3), it is seen that with the SQ-CH3F-Se method, for none of the isotopes, accurate results
were obtained, because of the remaining interference from
91, 92, 92
Zr+ (2) and from
92,94
Mo+ (3),
since these ions overlap with the mass of the reaction product ions formed in the reaction cell,
77
SeCH2+, 78SeCH2+ and 80SeCH2+, respectively (m/z-ratio = 91, 92 and 94). This method is unable
to overcome the interference since, in the SQ mode, all positive ions emerging from the plasma
enter the reaction cell. With the MS/MS-CH3F-Se method, 5 μg/L Se was obtained, since the
interfering ions, 91,92,94Zr+ (2) and 92,94Mo+ (3) are removed by Q1, (Q1 = 77, 78 and 80).
Page 49 of 65
Finally, for the simulated matrices containing 5 μg/L Se with 0.1 μg/L Ge (4) and 10 μg/L As (5),
respectively, accurate results were not obtained with the SQ-CH3F-Se method, which is due to the
method not being able to remove the interference from 72,73Ge19F+ (4) and from 75As19F+ (5), which
are formed in the reaction cell due to F atom transfer from the reaction gas CH3F, and the reaction
products thus formed again overlap with the masses of the Se reaction product ions formed in the
reaction cell,
77
SeCH2+,
78
SeCH2+ and
80
SeCH2+, respectively (m/z-ratio = 91, 92 and 94). This is
due no barrier being present before the reaction cell to avoid
72,73
Ge+ and
75
As+ from entering the
reaction cell. With the MS/MS-CH3F-Se method, 5 μg/L Se was again found for both (4 and 5).
This was, as was also the case for As, a result of Q1 being set at the mass of the original analytes
(78, 78 and 80, respectively), whereby the ions 72,73Ge+ and 75As+ were removed.
Thus, it was successfully demonstrated that the method using CH3F as reaction gas in the MS/MS
mode was the only method, which allowed for removal of all the interferences investigated. In
figure 30, a schematic representation shows how the different interferences are removed with the
MS/MS-CH3F-Se method for the interference-free determination of 77Se, 78Se and 80Se as 77SeCH2+,
78
SeCH2+ and 80SeCH2+, respectively.
Page 50 of 65
A)
B)
C)
Figure 30 Schematic representation of the operating principle of the Agilent 8800 instrument when using the MS/MS-CH3FSe method, leading to an interference-free determination of 77Se (A), 78Se (B) and 80Se (C) as 77SeCH2+, 78SeCH2+ and
80
SeCH2+ respectively. Modification of figure from[35].
Page 51 of 65
4.6 Results obtained for reference materials - As and Se
As a final validation, the methods for ICP-MS/MS using CH3F as reaction gas, MS/MS-CH3F-As
and MS/MS-CH3F-Se, were used to investigate 10 certified reference materials for As and 7
certified reference materials for Se. The certified reference materials investigated are listed in the
experimental section, table 4. For the determination of As, the digested samples could be diluted 40fold, while only a 20-fold dilution was possible for the Se-determination, due to the higher LODs
for the Se-method. For both methods, Te was used as internal standard (using the isotope 125Te) and
an external calibration curve was used in order to obtain the final concentrations. Te was chosen as
internal standard for both methods, instead of Se, which was used as internal standard when
measuring the simulated matrices for As, due to the fact that in several of the reference materials Se
is present, and when choosing an internal standard it is important that it is not already present in the
matrix. Additionally, Te has an ionization energy of 9.01 eV, thus it is similar to that of As and Se,
so it is expected that it is able to correct for the carbon effect (mentioned earlier in section 1) and
other matrix effects. In table 11 and table 12, the experimental values, (n = 20), obtained for the
certified reference materials for As and Se, respectively, are shown along with the standard
deviation (s), relative standard deviation (RSD), the 95 % confidence interval (CI 95 %) and the
certified values. The experimental values were obtained from measuring two different digested
samples, two times on different days and each measurement consisted of five consecutive
measurements for all reference materials (except for urine, which was not a digested sample). For
urine, four times five consecutive measurements over two days were performed on samples
prepared from the same reconstituted solution. In appendix 4 and 5, the results for the different
measurements, (n = 5), can be found.
Page 52 of 65
Table 11 Results obtained for the certified reference materials: the experimental values, standard deviation (s), relative
standard deviation (RSD), the 95 % confidence interval (CI 95 %) and the certified values for As. (n = 20)
Experimental
value (μg/g)
s (μg/g)
RSD (%)
CI 95 %
(μg/g)
Certified value
(μg/g)
NBS SRM 1575 Pine needles
0.2434
0.0063
2.6
0.0029
0.21 ± 0.04
NBS SRM 1573 Tomato leaves
0.3145
0.0130
4.1
0.0061
0.27 ± 0.05
NIST SRM 1568a Rice flour
0.2835
0.0097
3.4
0.0045
0.29 ± 0.03
CRM 526 Tuna fish tissue
4.954
0.068
1.4
0.032
4.8 ± 0.3
NRC-CNRC DORM-4 Fish protein
6.686
0.059
0.9
0.028
6.80 ± 0.64
BRC 414 Plankton
6.895
0.127
1.8
0.059
6.82 ± 0.28
NBS SRM 1646 Estuarine sediment
10.59
0.28
2.6
0.13
11.6 ± 1.3
NIST SRM 1566a Oyster tissue
13.79
0.19
1.4
0.09
14.0 ± 1.2
NRC-CNRC TORT-3 Lobster Hepatopancreas
SeronormTM Trace elements Urine, Level 1, Sero,
Norway
a
Unit for reference material, (μg/L), since it is not a solid.
66.94
0.41
0.61
0.19
59.5 ± 3.8
84.71a
0.82a
0.97
0.38a
79 ± 16a
Analyte: As
It can be seen from table 11 that when comparing the experimental values to the certified values for
As, no significant differences at a 95 % confidence level were found between the experimental
values and certified values for the certified reference materials, except for the certified reference
material NRC-CNRC TORT-3. Thus the accuracy of the method is good. As previously mentioned,
a significant difference is observed, at a 95 % confidence level, for the certified reference material
NRC-CNRC TORT-3, since the confidence intervals do not overlap. Different digestions were
prepared to try to resolve this, but similar results were obtained for different digestions.
Additionally, the reference material was also measured using the Element XR SF-ICP-MS, (n=10),
and the experimental value obtained was 67.8 ± 1.9 μg/g, which is in good agreement with the
result obtained using the MS/MS-CH3F-As method at a 95 % confidence level. Thus, the problem
either lies in the digestion process or there is a problem with the reference material caused by
contamination. This was however not further investigated due to lack of time. Furthermore, it can
be seen that the experimental values obtained for the certified reference materials are both below
and above the certified values, thus there is no tendency to always obtain values that are higher or
lower than the certified value with the method, which is good.
Additionally, from the table it can be seen that the standard deviations on the experimental values
are low, which can better be seen by looking at the RSD, which range between 0.61 - 4.1 %, so
even for low values of As, the RSD is low. This means that the precision of the method, a measure
for how close the measurements are to one another[47], is good. Additionally it also shows that the
reproducibility of the method, thus how close results of repeated measurements of a couple of
Page 53 of 65
samples, prepared from the same material and by the same procedure, are to each other[47], is good,
since the results are obtained by measuring 2 digestions of the same material on two different days.
Table 12 Results obtained for the certified reference materials and the certified values for Se. (n = 20)
Analyte: Se
Experimental
value (μg/g)
0.352
s (μg/g)
CI 95 %
(μg/g)
0.018
Certified
value (μg/g)
0.039
RSD
(%)
10.9
78
80
0.3528
0.0199
5.6
0.0093
0.38 ± 0.04
77
0.3513
0.0104
3.0
0.0049
0.638
0.041
6.4
0.019
78
0.634
0.032
5.0
0.015
80
0.6543
0.0196
3.0
0.0092
77
1.753
0.085
4.9
0.040
78
1.721
0.046
2.7
0.022
80
1.771
0.027
1.5
0.013
77
2.233
0.091
4.1
0.043
78
2.215
0.055
2.5
0.026
80
2.224
0.036
1.6
0.017
77
3.647
0.097
2.7
0.046
78
3.643
0.066
1.8
0.031
80
3.626
0.032
0.87
0.015
77
11.03
0.22
2.0
0.10
78
11.087
0.091
0.82
0.043
80
11.073
0.115
1.0
0.054
77
0.94
b
5.6
0.44b
0.61
b
3.7
0.29b
0.28b
1.7
0.13b
Isotope
77
Se
NIST SRM 1568a Rice flour
Se
Se
Se
NBS SRM 1646 Estuarine sediment
Se
Se
Se
BRC 414 Plankton
Se
Se
Se
NIST SRM 1566a Oyster tissue
Se
Se
Se
NRC-CNRC DORM-4 Fish protein
Se
Se
Se
NRC-CNRC TORT-3 Lobster Hepatopancreas
Se
Se
16.98
b
78
16.36
b
80
16.87b
Se
SeronormTM Trace elements Urine, Level 1, Sero,
Norway
Se
Se
a
b
(0.6)a
1.75 ± 0.10
2.21 ± 0.24
3.56 ± 0.34
10.9 ± 1.0
13.9 ± 2.8b
Non-certified concentration of constituent element
Unit for reference material, (μg/L), since it is not a solid
Also for Se, it can be seen from table 12, that, at a 95 % confidence level, no significant differences
were found between the experimental values and certified values for all certified reference
materials. Thus, the accuracy of this method is also good. Furthermore, it can be seen that for all
reference materials for Se, the standard deviations and the RSDs, which range between 0.82 - 10.9
%, are acceptable. This again means that the precision and the reproducibility of this method were
good. It can be seen that s and RSD are in general higher for 77Se followed by 78Se, while the results
based on
80
Se show the lowest s values and RSDs. This is due to the higher sensitivity for
followed by that for 78Se and 77Se.
Page 54 of 65
80
Se,
Furthermore, from the experimental values it can be seen, that both lower and higher values are
found in comparison to the certified values, which again is good, since if this tendency was present,
this could indicate that a systematic error was present.
Additionally, it can be seen that the same results are obtained for the 3 isotopes, thus this opens up
possibilities for performing isotopic analysis. Due to lack of time, this was however not further
investigated, but it would be interesting to investigate in a future project.
Page 55 of 65
5. Conclusion
In this project, methods for an interference-free determination of As and Se at ultra-trace levels
using the ICP-MS/MS technique with CH3F as reaction gas have been successfully developed,
optimized and validated. This was feasible due to the possibility of performing a product ion scan
with the ICP-MS/MS technique, which made it possible to easily identify reaction products,
something which is more difficult with the traditional Q-ICP-MS systems.
It was shown that a low LOD could be obtained for both target elements, obtaining the lowest LOD
that has ever been obtained for As to the knowledge of the author and obtaining LODs for Se
similar to those reported for SF-ICP-MS and it is believed that the LODs for Se could be improved
further if higher flows of CH3F could be used. An evaluation of the methods using simulated
matrices demonstrated that it was possible to overcome interferences that typically cannot be
removed with other quadrupole-based methods and to overcome new interferences, which could
interfere at the mass of the reaction product ion, due to use of the mass-shift mode. Furthermore, it
was possible to determine Se using the three isotopes
77,78,80
Se, where e.g., the isotope
80
Se, the
most abundant isotope, is typically not accessible via SF-ICP-MS, since this technique is not able to
completely resolve the argon-based interference. This result is also promising in the context of
isotopic analysis. Thus, the methods developed match, and in some cases even exceed the
capabilities of SF-ICP-MS, which typically is the method of choice for the determination of As and
Se.
As a proof of concept, the methods were successfully used for the determination of As and Se in
reference materials of various biological and environmental origin and similar results were obtained
for the three Se - isotopes investigated.
Outlook
In future work, it would be interesting to apply the methods to real samples and to develop methods
where speciation of As and Se species is possible, since, as mentioned in the introduction, different
species of As and Se have different toxicity. Additionally it would be interesting to develop a
method for simultaneous determination of As and Se.
Page 56 of 65
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7. Appendix
Appendix 1: All parameters and instrument settings used for the methods As: MS/MS-CH3F-As, MS/MS-no
gas-As, MS/MS-He-As and SQ-CH3F-As and Se: MS/MS-CH3F-Se, MS/MS-He-Se and SQ-CH3F-Se.
Scan type
Plasma mode
RF power
RF Matching
Sample Depth
Carrier gas
Nebulizer pump
S/C Temp
Extract 1
Extract 2
Omega Bias
Omega Lens
Q1 entrance
Q1 Exit
Cell focus
Cell Entrance
Cell Exit
Deflect
Plate Bias
Q1 mass gain
Q1 mass offset
Q1 axis gain
Q1 axis offset
Q1 Bias
Q1 Prefilter Bias
Q1 Postfilter
Reaction gas flow rate
Octopole Bias
Octopole RF
Energy discrimination
Q2 mass gain
Q2 mass offset
Q2 axis gain
Q2 axis offset
Q2 QP Bias
Torch H
Torch V
Discriminator
Analog HV
Pulse HV
Q1→ Q2
Wait time offset
Nr. Replicates
Nr. Sweep replicates
Integration time
Page 61 of 65
CH3F
MS/MS or SQ
Low matrix
1550 W
1.80 V
5.5 mm
1.18 L/min
0.20 rps
2 °C
-3.0 V
-185.0 V
-100 V
9.4 V
1V
0V
2.0 V
-48 V
-60 V
4.0 V
-60 V
126
126
0.9989
0.11
-2.0 V
-14.0 V
-22.0 V
72 %
-4.1 V
140 V
-8.4 V
128
127
1.0001
-0.01
-12.5 V
0.0 mm
0.2 mm
4.5 mV
1651 V
1059 V
75 → 89
78 → 78
125 → 125
2 ms
10
100
1s
→ 89
→ 78
Analyte: As
No gas
MS/MS
Low matrix
1550 W
1.80 V
5.5 mm
1.18 L/min
0.20 rps
2 °C
-3.0 V
-175.0 V
-95 V
10.2 V
0V
-7 V
-1.0 V
-46 V
-60 V
12.8 V
-45 V
126
126
0.9989
0.11
-1.0 V
-18.0 V
-34.0 V
-4.1 V
150 V
-8.4 V
128
127
1.0001
-0.01
-12.5 V
0.0 mm
0.2 mm
4.5 mV
1651 V
1059 V
He
MS/MS
Low matrix
1550 W
1.80 V
8.0 mm
1.05 L/min
0.10 rps
2 °C
0.0 V
-195.0
-105 V
9.6 V
-5 V
-1 V
0.0 V
-46 V
-70 V
-2.2 V
-60 V
126
126
0.9989
0.11
0.0 V
-18.0 V
-20.0 V
4.0 mL/min He
-18.0 V
160 V
5.0 V
128
127
1.0001
-0.01
-13.0 V
0.0 mm
0.2 mm
4.5 mV
1651 V
1059 V
75 → 75
78 → 78
75 → 75
78 → 78
2 ms
10
100
1s
2 ms
10
100
1s
Analyte: Se
CH3F/He
He
MS/MS or SQ
MS/MS
Low matrix
Low matrix
1550 W
1550 W
1.80 V
1.80 V
4.5 mm
4.5 mm
1.13 L/min
1.13 L/min
0.20 rps
0.20 rps
2 °C
2 °C
-3.9 V
-3.9 V
-195.0 V
-195.0 V
-95 V
-105 V
11.3 V
11.5 V
-4 V
-12 V
0V
-1V
4.0 V
0.0 V
-48 V
-50 V
-56 V
-70 V
2.6 V
-3.2 V
-60 V
-60 V
126
126
126
126
0.9989
0.9989
0.11
0.11
-1.0 V
0.0 V
-20.0 V
-12.0 V
-38.0 V
-38.0 V
100 %
4.0 mL/min He
-4.1 V
-18.0 V
190 V
180 V
-8.4 V
5.0 V
128
128
127
127
1.0001
1.0001
-0.01
-0.01
-12.5 V
-13.0 V
0.2 mm
0.2 mm
0.2 mm
0.2 mm
4.5 mV
4.5 mV
1662 V
1662 V
1072 V
1072 V
77 → 91
→ 91
77 → 77
78 → 92
→ 92
78 → 78
80 → 94
→ 94
80 → 80
125 → 125 → 125
125 → 125
2 ms
2 ms
10
10
100
100
1s
1s
Appendix 2: Calibration curves for As: MS/MS-CH3F-As, MS/MS-no gas-As, MS/MS-He-As and SQCH3F-As and Se: MS/MS-CH3F-Se, MS/MS-He-Se and SQ-CH3F-Se, as well as for Element XR, SF-ICPMS. (n = 10)
Page 62 of 65
Appendix 3: Calibration curves for MS/MS-CH3F-As and MS/MS-CH3F-Se using 6 % MeOH and 94%
HNO3. (n = 10)
Page 63 of 65
Appendix 4: Results obtained for the certified reference material for As, where 1 - 4 indicate different
analyses, each consisting of 5 consecutive measurements. (n = 5)
NBS SRM 1575 Pine needles
1
2
3
4
0.2337-0.2564
0.2443-0.2522
0.2312-0.2438
0.2390-0.2493
Exp. value
(μg/g)
0.2434
0.2473
0.2374
0.2452
NBS SRM 1573 Tomato leaves
1
2
3
4
0.2994-0.3142
0.2990-0.3113
0.3078-0.3242
0.310-0.342
0.3066
0.3041
0.3167
0.331
0.0053
0.0053
0.0060
0.013
1.7
1.7
1.9
4.0
0.0066
0.0066
0.0074
0.016
NIST SRM 1568a Rice flour
1
2
3
4
0.2747-0.2934
0.2797-0.2981
0.2834-0.2986
0.2683-0.2756
0.2833
0.2886
0.2904
0.2718
0.0092
0.0074
0.0060
0.0027
3.2
2.6
2.1
1.0
0.0114
0.0092
0.0074
0.0034
CRM 526 Tuna fish tissue
1
2
3
4
4.835-4.940
4.925-5.030
4.862-5.064
4.975-5.072
4.879
4.965
4.957
5.015
0.038
0.044
0.072
0.038
0.78
0.89
1.5
0.76
0.048
0.055
0.090
0.048
NRC-CNRC DORM-4 Fish protein
1
2
3
4
6.618-6.728
6.577-6.813
6.634-6.776
6.663-6.750
6.675
6.663
6.714
6.694
0.050
0.091
0.051
0.038
0.74
1.4
0.76
0.56
0.062
0.113
0.064
0.047
BRC 414 Plankton
1
2
3
4
6.973-7.089
6.715-6.900
6.828-6.967
6.67-6.92
7.058
6.815
6.907
6.80
0.049
0.079
0.051
0.11
0.70
1.2
0.74
1.6
0.061
0.098
0.063
0.14
NBS SRM 1646 Estuarine sediment
1
2
3
4
10.771-10.923
10.621-10.867
10.01-10.31
10.39-10.85
10.836
10.747
10.18
10.59
0.071
0.087
0.12
0.18
0.66
0.81
1.2
1.7
0.089
0.108
0.15
0.23
NIST SRM 1566a Oyster tissue
1
2
3
4
13.66-13.97
13.543-13.621
13.67-14.16
13.71-14.08
13.79
13.577
13.93
13.87
0.14
0.035
0.20
0.17
1.0
0.26
1.4
1.2
0.17
0.044
0.25
0.21
1
2
3
4
66.58-66.88
66.19-67.12
67.03-67.74
66.43-67.37
66.73
66.61
67.38
67.03
0.11
0.33
0.29
0.37
0.16
0.50
0.43
0.55
0.14
0.42
0.36
0.46
1
2
3
4
84.02-86.77a
83.96-86.19a
83.49-85.61a
83.96-84.41a
84.98a
84.96a
84.76a
84.13a
1.10a
0.83a
0.81a
0.20a
1.3
0.98
0.95
0.24
1.37a
1.04a
1.00a
0.25a
Analyte: As
NRC-CNRC TORT-3 Lobster Hepatopancreas
Seronorm
a
TM
Trace elements Urine, Level 1, Sero, Norway
Range (μg/g)
Unit for reference material, (μg/L), since it is not a solid.
Page 64 of 65
s (μg/g)
RSD (%)
CI (μg/g)
0.0083
0.0030
0.0047
0.0045
3.4
1.2
2.0
1.8
0.0103
0.0037
0.0058
0.0056
Certified value
(μg/g)
0.21 ± 0.04
0.27 ± 0.05
0.29 ± 0.03
4.8 ± 0.3
6.80 ± 0.64
6.82 ± 0.28
11.6 ± 1.3
14.0 ± 1.2
59.5 ± 3.8
79 ± 16a
Appendix 5: Results obtained for the certified reference material for Se, where 1 - 4 indicate different analyses, each consisting of 5 consecutive
measurements. (n = 5)
77
78
Se
NIST SRM 1568a rice flour
NBS SRM 1646 Estuarine
sediment
1
2
3
4
0.644-0.695
0.529-0.656
0.586-0.652
0.605-0.696
0.671
0.615
0.616
0.648
0.021
0.051
0.027
0.038
3.1
8.4
4.3
5.8
0.026
0.064
0.033
0.047
0.599-0.669
0.597-0.660
0.583-0.667
0.600-0.707
0.633
0.637
0.615
0.652
0.029
0.024
0.031
0.039
4.6
3.8
5.1
5.9
0.036
0.030
0.039
0.048
0.634-0.688
0.628-0.680
0.636-0.694
0.621-0.658
0.657
0.653
0.662
0.645
0.023
0.020
0.021
0.015
3.5
3.1
3.2
2.3
0.028
0.025
0.027
0.018
(0.6)a
BRC 414 Plankton
1
2
3
4
1.632-1.815
1.701-1.791
1.58-1.95
1.696-1.827
1.737
1.730
1.80
1.750
0.076
0.036
0.14
0.058
4.4
2.1
8.0
3.3
0.094
0.045
0.18
0.072
1.652-1.827
1.666-1.771
1.665-1.747
1.667-1.791
1.736
1.723
1.699
1.726
0.063
0.038
0.031
0.053
3.6
2.2
1.8
3.1
0.078
0.047
0.039
0.066
1.729-1.801
1.724-1.804
1.751-1.823
1.730-1.778
1.772
1.759
1.790
1.763
0.030
0.030
0.027
0.019
1.7
1.7
1.5
1.1
0.037
0.037
0.033
0.024
1.75 ± 0.10
NIST SRM 1566a Oyster
tissue
1
2
3
4
2.12-2.40
2.15-2.45
2.157-2.310
2.075-2.331
2.23
2.25
2.230
2.220
0.11
0.12
0.059
0.095
5.1
5.2
2.7
4.3
0.14
0.14
0.074
0.117
2.163-2.348
2.212-2.270
2.149-2.286
2.135-2.213
2.243
2.239
2.203
2.173
0.070
0.025
0.061
0.034
3.1
1.1
2.8
1.6
0.087
0.032
0.075
0.043
2.181-2.284
2.208-2.289
2.184-2.255
2.178-2.213
2.246
2.234
2.224
2.191
0.043
0.032
0.028
0.015
1.9
1.4
1.2
0.67
0.054
0.040
0.034
0.018
2.21 ± 0.24
NRC-CNRC DORM-4 Fish
protein
1
2
3
4
3.538-3.798
3.604-3.725
3.53-3.79
3.41-3.75
3.645
3.687
3.64
3.62
0.097
0.051
0.11
0.13
2.7
1.4
3.1
3.7
0.120
0.064
0.14
0.16
3.592-3.792
3.635-3.697
3.595-3.747
3.504-3.614
3.657
3.670
3.673
3.574
0.079
0.023
0.064
0.043
2.2
0.63
1.8
1.2
0.098
0.029
0.080
0.053
3.594-3.669
3.574-3.671
3.590-3.682
3.575-3.652
3.638
3.614
3.631
3.623
0.027
0.037
0.035
0.031
0.76
1.0
0.98
0.86
0.034
0.046
0.044
0.039
3.56 ± 0.34
NRC-CNRC TORT-3
Lobster Hepatopancreas
1
2
3
4
10.74-11.38
11.00-11.38
10.82-11.04
10.63-11.02
11.20
11.14
10.90
10.88
0.26
0.16
0.10
0.15
2.3
1.4
0.93
1.4
0.32
0.20
0.13
0.19
11.004-11.178
10.86-11.24
10.941-11.161
11.024-11.230
11.112
11.08
11.057
11.099
0.065
0.14
0.081
0.084
0.59
1.3
0.73
0.75
0.081
0.17
0.100
0.104
11.157-11.257
10.982-11.124
10.992-11.173
10.82-11.20
11.211
11.033
11.057
10.99
0.036
0.057
0.071
0.14
0.32
0.52
0.64
1.2
0.045
0.071
0.088
0.17
10.9 ± 1.0
SeronormTM Trace
elements Urine, Level 1, ref.
9067 - Sero, Norwayb
1 15.17-17.112
2 15.52-18.38
3 15.92-17.49
4 16.56-18.75
16.26
17.11
16.80
17.74
0.76
1.04
0.61
0.87
4.7
6.1
3.6
4.9
0.94
1.30
0.76
1.08
15.66-16.77
16.00-17.77
15.51-17.312
15.25-16.51
16.47
16.65
16.31
16.02
0.46
0.69
0.76
0.48
2.8
4.1
4.7
3.0
0.57
0.85
0.95
0.59
16.52-17.21
16.39-17.55
16.72-17.02
16.46-17.00
16.80
17.03
16.86
16.81
0.26
0.46
0.13
0.22
1.5
2.7
0.74
1.3
0.32
0.57
0.16
0.28
13.9 ± 2.8b
a
b
0.027
0.036
0.034
0.037
7.0
9.8
10.1
11.5
Non-certified concentration of constituent element
Unit for reference material, (μg/L), since it is not a solid
Page 65 of 65
s
(μg/g)
RSD
(%)
0.3290-0.3492
0.331-0.361
0.326-0.401
0.347-0.381
Exp.
Value
(μg/g)
0.3381
0.345
0.362
0.365
0.0079
0.012
0.027
0.016
Range (μg/g)
2.3
3.5
7.6
4.5
CI 95
%
(μg/g)
0.0098
0.015
0.034
0.020
0.3462-0.3654
0.323-0.350
0.3415-0.3681
0.3418-0.3600
Exp.
Value
(μg/g)
0.3593
0.343
0.3544
0.3484
Se
0.337-0.397
0.329-0.415
0.293-0.379
0.260-0.349
Range (μg/g)
RSD
(%)
80
1
2
3
4
Analyte: Se
s
(μg/g)
CI 95
%
(μg/g)
0.033
0.045
0.042
0.046
Se
Exp.
Value
(μg/g)
0.380
0.367
0.339
0.323
Range (μg/g)
s (μg/g)
RSD
(%)
CI 95 %
(μg/g)
Certified
value (μg/g)
0.0077
0.012
0.0094
0.0073
2.1
3.4
2.7
2.1
0.0095
0.014
0.0117
0.0091
0.38 ± 0.04
Interference-free determination of ultra-trace levels of Arsenic and Selenium using
methyl fluoride as reaction gas in ICP-MS/MS
E. S. Nissen, E. Bolea-Fernandez, L. Balcaen, and F. Vanhaecke
Department of Analytical Chemistry, Ghent University, Belgium
Determination of As and Se at ultra-trace levels using ICP-mass
spectrometry (ICP-MS) is a challenging task due to the presence of
spectral overlap. In this work, the use of methyl fluoride (a mixture
of 10 % CH3F and 90 % of He) was tested as reaction gas in ICPMS/MS for its capabilities for accurate and precise determination
of As and Se. Using product ion scans, the main reaction product
ions were identified (AsCH2+ and SeCH2+) and relied on to
measure As and Se at a different and interference-free m/z-ratio
with a limit of detection of 0.5 and 7 ng/L, respectively. To check
the potential of the CH3F methods for the analysis of samples with
a heavy matrix, matrix-matched standard solutions were analyzed,
whereby it was proven that the CH3F methods allow interferencefree determination of both analytes in all cases. Finally, a set of
diverse certified reference materials were measured in order to
validate the true potential of the methods. All results were in good
agreement with the certified values and/or the values obtained by
means of sector-field ICP-MS.
Keywords: Arsenic, Selenium, ICP-MS/MS, Methyl fluoride
1. Introduction
Arsenic and selenium are present in the environment through both natural and
anthropogenic routes as a result of agricultural, industrial and mining activities.[1,2] Both
are present in inorganic and organic forms and in various oxidation states (-III, 0, +III,
+V for As and +VI, +IV, 0, -II for Se). Arsenic is known to be a toxin, whereas Se is an
essential element, but becomes toxic at higher concentrations, while the difference
between an appropriate and an excessive concentration is small.[3-5] The different
species of As and Se found in the environment have different toxicities and inorganic
species are known to be more toxic than organic species.[3,6] Thus, it is important to be
able to determine As and Se at ultra-trace levels with high accuracy.
Arsenic and selenium have been investigated earlier using a variety of analytical
techniques, such as atomic absorption spectrometry (AAS) [7-9], atomic fluorescence
spectrometry (AFS) [10-12], and inductively coupled plasma-atomic emission
spectrometry (ICP-AES). [13-15] However, inductively coupled plasma-mass
spectrometry (ICP-MS) has to be considered as the technique of choice for the
determination of As and Se, owing to very low detection limits, a wide linear dynamic
range, as well as multi-element and isotopic capabilities.[3,6,16-19] However, the
determination of As and Se in a complex matrix using this technique remains a challenge
due to the following reasons i) As and Se have high ionization energies (9.82 eV and 9.75
eV, respectively), which means that they are poorly ionized under normal ICP-MS
1
conditions, leading to poor sensitivity for the elements, and ii) As and Se suffer from
spectral overlap, as a result of the occurrence of, e.g., isobaric, polyatomic and doubly
charged ions. See Table I for a list of possible interferences.
TABLE I. As and Se - isotopes with their natural isotopic abundance [20] and the most important isobaric, polyatomic
and doubly charged interferences [21,22] (non-restrictive list).
Abundance
Isobaric
Doubly charged
Analyte
Polyatomic interference
(%)
interference
interference
40
75
+
100
74
Se+
0.89
74
76
9.37
76
As
Se+
-
Ge+
Ar35Cl+, 59Co16O+, 36Ar38ArH+, 38Ar37Cl+,
Ar39K+, 43Ca16O2+, 40Ar 23Na12C+, 12C31P16O2+,
40
Ca35Cl+
36
37
Cl37Cl+, 36Ar38Ar+, 38Ar36S+, 40Ar34S+, 39K35Cl+,
58
Ni16O+
40
Ar36Ar+, 38Ar38Ar+, 60Ni16O+, 39 K37Cl+,
41 35 +
K Cl
Ge+
Nd2+, 150Eu2+,
150
Sm2+
148
Sm2+, 148Nd2+
152
Sm2+, 152Gd2+
38
77
+
Se
Se+
-
7.63
78
23.77
78
80
49.61
80
82
8.73
82
Se+
Se+
Ar39K +, 61Ni16O+, 59Co18O+, 40Ar37Cl+, 40Ca37Cl+
36
40
+ 38
Ar ArH , Ar2H+, 12C19F14N16O2+
38
Ar 40Ca+, 62Ni16O+, 41K37Cl+, 40Ar 38Ar+
150
Kr+
Kr+
Kr+
40
154
Sm2+, 154Gd2+
156
Gd2+, 156Dy2+
Ar 40Ca+, 64Ni16O+, 64Zn16O+, 32S216O+, 32S16O3+,
40
Ar40Ar+, 40Ca40Ca+,
160
Ar 42Ca+,34S16O3+,
164
40
66
Zn16O+, 12C35Cl2+, 40Ar2H2+
Gd2+, 160Dy2+
Dy2+, 164Er2+
In literature, a variety of approaches have been proposed to tackle these problems.
With regard to the problem of poor ionization, several studies have used the addition of
carbon as a mean of increasing the signal intensity, which is mainly due to the charge
transfer reaction, where C+ species transfer their charge to As and Se atoms, but also due
to e.g., an enhancement of the nebulization efficiency for the sample.[23] In literature,
enhancements of more than 150 % for As and Se using methanol have been reported.[18]
However, the carbon effect can also be a problem in the analysis if the sample contains
large amounts of carbon and proper correction, by using a suitable internal standard, by
adding organic solvents to both standard and samples or by using standard addition for
calibration, is necessary.[24]
The problem of spectral overlap has mainly been dealt with in two ways. One option
is to use an SF-ICP-MS instrument, where higher mass resolution is used to overcome
spectral overlap. However, this instrument comes at a high purchase price and obtaining
the highest mass resolution (necessary to determine As and Se), is accomplished with a
loss in sensitivity of 2 orders of magnitude.[ 19] Another option is to use a quadrupolebased ICP-MS instrument equipped with a collision/reaction cell, where chemical
resolution is used to deal with spectral overlap. Interferences can be removed by collision
using, e.g., a gas mixture such as He/H2, though this also reduces the transmission of As+
and Se+ [16,19], or by using a reaction gas such as O2, which can either react with the
interfering ion or with the analyte ion, whereby the analyte ion can be determined
interference-free in the on-mass mode or in the mass-shift mode, respectively [25,26].
In 2013, a new generation of quadrupole-based ICP-MS instrumentation was
introduced, ICP-MS/MS, where an octopole-based collision/reaction cell is placed inbetween two quadrupole mass analyzers. The introduction of the first quadrupole allows
only the analyte ions and other on-mass ions to pass to the cell. Thus, the processes
taking place in the collision/reaction cell are more under control and additionally, this setup enables the possibility to perform a product ion scan, which can aid in the
2
identification of reaction products formed in the cell. Thus the operation in the MS/MS
mode should deal better with spectral overlap and opens up the possibility to use more
unconventional reaction gases, such as CH3F.[19,27] CH3F can react with an ion
according to 5 main reaction paths [28] and thus, it is difficult to predict which will be the
main reaction path for the different analytes.
The main goal of this project is to investigate the capabilities of CH3F as reaction gas
in ICP-MS/MS to resolve the spectral overlap that As and Se suffer from, with the aim of
developing sensitive and selective methods for the determination of As and Se at ultratrace levels in diverse samples.
2. Experimental
2.1 Instrumentation
To carry out all measurements, an Agilent 8800 triple quadrupole ICP-MS instrument
(ICP-QQQ/Agilent technologies, Japan) was used. The instrument is equipped with an
introduction system, comprising of a concentric nebulizer and a Scott-type double-pass
spray chamber, and a mass separation device, comprising of two quadrupole mass
analyzers with an octopole-based collision/reaction cell fitted in-between (Figure 1). The
instrument can be operated in the "vented mode" (no gas in the cell) or the cell can be
pressurized with a collision gas (e.g., He) or a reaction gas (e.g., H2, O2, NH3) or a
mixture of both.
Figure 1. Schematic overview of the operation principle of the ICP-MS/MS, where a general example is given for the
interference-free determination of XM+ as XMCH2+, where M = analyte, N = interference, X = mass, Y = mass ≠ X.
Modification of figure from [27].
In this project a rather unconventional reaction gas was used, CH3F/He in a 10/90 %
mixture, which was introduced via the 4rd gas inlet. The gas flow rate is controlled by a
mass flow controller, which is calibrated for O2, and allows a flow of 0 - 100 %, which is
equivalent to 0 - 1 mL/min O2. The analytes 75As and 77, 78, 80Se were monitored.
SF-ICP-MS, which was - until now - the method of choice for the determination of
low levels of As and Se, was used for validation purposes. The instrument used is a
Thermo Element XR SF-ICP-MS (Thermo-Scientific, Germany).
The most important settings and parameters can be found in Table II for the Agilent
8800 ICP-QQQ and in Table III for the Thermo Element XR SF-ICP-MS.
3
TABLE II. Instrument settings for the Agilent 8800 ICP-QQQ instrument when measuring As and Se.
Agilent 8800
Analyte: As
Analyte: Se
CH3F
No gas
He
CH3F
He
Scan type
MS/MS
SQ
MS/MS
MS/MS
MS/MS SQ
MS/MS
Plasma mode
Low matrix
Low matrix
Low matrix
Low matrix
Low matrix
RF power
1550 W
1550 W
1550 W
1550 W
1550 W
Carrier gas flow rate
1.18 L/min
1.18 L/min
1.05 L/min
1.13 L/min
1.13 L/min
Reaction gas flow rate
72 %
4.0 mL/min He
100 %
4 mL/min He
Q1 Bias
-2.0 V
-1.0 V
0.0 V
-1.0 V
0.0 V
Octopole Bias
-4.1 V
-4.1 V
-18.0 V
-4.1 V
-18.0 V
Energy discrimination
-8.4 V
-8.4 V
5.0 V
-8.4 V
5.0 V
Q2 axis offset
-0.01
-0.01
-0.01
-0.01
-0.01
Q2 Bias
-12.5 V
-12.5 V
-13.0 V
-12.5 V
-13.0 V
77 → 91 → 91
77 → 77
75 → 89 → 89
75 → 75
75 → 75
78 → 92 → 92
78 → 78
Q1→ Q2
78 → 78 → 78
78 → 78
78 → 78
80 → 94 → 94
80 → 80
125 → 125
125 → 125 → 125
125 → 125
Wait time offset
2 ms
2 ms
2 ms
2 ms
2 ms
Nr. Replicates
10
10
10
10
10
Nr. Sweep replicates
100
100
100
100
100
Integration time
1s
1s
1s
1s
1s
TABLE III. Instrument settings for the Thermo Element XR SF-ICP-MS instrument when measuring As and Se.
Element XR
Scan type
EScan
Resolution
High
RF power
1200 W
Carrier gas flow rate
0.975 L/min
Mass window
100 %
Search window
70 %
Integration window
60 %
Sample time
0.01 s
Sample/peak
20
75
Nuclides monitored
As, 77Se, 78Se, 125Te
Total analysis time / sample
180 s
2.2 Samples and reagents
Standard solutions used to obtain calibration data were prepared from elemental
standard solution of 1 g/L As (PlasmaCal, SCP Science, Canada) and 10 g/L Se (Aldrich
chemical company inc., USA). External calibration curves were prepared by preparing a
set of 5 standard solutions in the concentration range 0 - 5 μg/L of As and Se. For sample
preparation, high purity reagents were used. Water was purified by a Direct Q-3 Milli-Q
system (Millipore, USA) and HNO3 (14 M, pro analysis, Chemlab, Belgium) was
prepared by purification using a Teflon® sub-boiling distillation set-up (Cupola still,
PicoTrace®).
For the matrix-matched standard solutions, elemental standard solutions of 1 g/L of
Nd and Zr (PlasmaCal, SCP Science, Canada), 1 g/L of Ca, Y, Ge and Zn (Inorganic
Ventures, The Netherlands) and 1 g/L of Mo, Gd and Sm (Alfa Aesar, Germany) and HCl
(12 M, trace analysis, Chemlab, Belgium) were used, and dilution was performed with
0.14 M HNO3.
For acid digestion, H2O2 (9.8 M, Trace select, Fluka, Belgium) and HF (28 M, trace
analysis, Fisher Chemicals, Great Britain) were used together with 14 M HNO3.
4
Selenium and tellurium (1 g/L, PlasmaCal, SCP Science, Canada) were used as
internal standards for measuring As. For the analysis of Se, only Te was used as internal
standard.
The methods for the determination of As and of Se were validated using a diversity of
certified reference materials listed in table IV.
TABLE IV. List of certified reference materials investigated along with their certified values for As and Se.
Certified value (μg/g)
Certified reference material
NBS SRM 1575 Pine needles
NBS SRM 1573 Tomato leaves
NIST SRM 1568a Rice flour
CRM 526 Tuna fish tissue
NRC-CNRC DORM-4 Fish protein
BRC 414 Plankton
NBS SRM 1646 Estuarine sediment
NIST SRM 1566a Oyster tissue
NRC-CNRC TORT-3 Lobster Hepatopancreas
SeronormTM Trace elements Urine, Level 1, Sero, Norway
a
b
As
0.21 ± 0.04
0.27 ± 0.05
0.29 ± 0.03
4.8 ± 0.3
6.80 ± 0.64
6.82 ± 0.28
11.6 ± 1.3
14.0 ± 1.2
59.5 ± 3.8
79 ± 16b
Se
0.38 ± 0.04
3.56 ± 0.34
1.75 ± 0.10
(0.6)a
2.21 ± 0.24
10.9 ± 1.0
13.9 ± 2.8b
Non-certified concentration of constituent element
Unit of reference material, (μg/L), since it is not a solid
2.3 Sample preparation
The solid reference materials were prepared for analysis by digestion, whereas the
reference material urine was prepared by reconstitution of the material. Tellurium was
added as internal standard to all samples. In order to avoid problems with stability of the
solutions and to reduce the risk of contamination of the samples, all samples were
measured within 24 h after sample preparation.
2.3.1 Digestion procedure Digestion was performed by accurately weighing (range:
0.0800 - 0.2200 g) certified reference material into a Savillex®vessel, to which 4 mL of
14 M HNO3 and 1 mL of 9.8 M H2O2 was added. In case of sediment, an additional 1 mL
of 28 M HF was added to the material to fully digest the sample. The mineralization was
carried out overnight at 110 °C on a hot plate. Furthermore, in each set of digestions,
blanks were included. The samples were stored at 5 °C until analysis. For the
determination of As and Se a 40-fold and a 20-fold dilution of the samples was
performed, respectively, in order to reduce the concentration of the concentrated acids
and the matrix elements. For Se a lower dilution factor was preferred because of the
lower sensitivity for this element.
2.3.2 Reconstitution procedure In order to analyze the freeze dried SeronormTM
reference material, the urine was reconstituted following the procedure given by the
supplier and the sample was stored at 5 °C until analysis. For the determination of As and
Se a 20-fold dilution was performed to reduce the matrix load.
5
3. Results and discussion
Through the years, different approaches have been used for the determination of As and
Se using Q-ICP-MS equipped with a collision/reaction cell. These approaches often use
more conventional gases, such as He, H2, O2 and CH4, since these have proven to be
useful and it is relatively straightforward to predict the reaction path of these gases.[29]
However for more unconventional gases such as CH3F, five main reaction paths exist and
higher order reaction products can also be formed.[28] It is first with introduction of ICPMS/MS that it has become relatively easy and straightforward to use such a gas, since the
product ion scan enables easy determination of the main reaction product(s) formed in the
cell. In this work, methods for determining As and Se using CH3F as reaction gas were
developed and compared with methods using the more conventional collision gas He and
using no gas, by comparing analytical performance and the ability to overcome spectral
interferences. Likewise, comparisons were also made with SF-ICP-MS. Further
validation of the methods using CH3F was done by analyzing a set of various reference
materials.
3.1 Optimization of the ICP-MS/MS protocol for the determination of As and Se
In order to evaluate the use of CH3F as a reaction gas for the determination of As and
Se in MS/MS mode, product ion scans were performed in order to identify the main
reaction product for a 5 μg/L As and a 5 μg/L Se standard solution. For this purpose, the
m/z-ratio of Q1 was set at the mass of the original ion, while Q2 scanned over the entire
mass range from 0 - 260 amu. Four product ion scans were recorded at cell gas flow rates
of 25, 50, 75 100 %, and figure 2 displays the scans at a flow rate of 75 % for As and of
100 % for Se, since at these flows the highest signal intensity was observed for the main
reaction products.
Figure 2. Product ion scans for A) As, at a flow of 75 %, and for B) Se, at a flow of 100 % of the maximum flow rate.
It can be seen from the figure that below the m/z-ratio of the original analyte ion,
charge-transfer product ions, such as CH3+, CH2F+ and C2H6F+, occur. These cannot be
used to determine As and Se, since they are not only formed by charge transfer from As
and Se, respectively, but also from other ions present in the reaction cell. Furthermore,
the original analyte ions, As+ and Se+, can also not be used, since they suffer from
spectral interferences. Thus, the only appropriate ions to use are the reaction product ions
with the highest signal intensity. For As this is 75AsCH2+ and for Se this is 80SeCH2+.
Thus, As and Se react in a similar way with CH3F, i.e. HF elimination. The CH3F flow
was optimized by performing a ramp cell gas scan, where a 0.14 M HNO3 blank solution
6
and a 5 μg/L standard solution of As and of Se were measured at flow rates between 0 100 %, with the optimal flow being the one providing the highest signal-to-background
ratio. At a flow rate of 72 % for As and of 100 % for Se, the maximum sensitivity was
obtained. All other parameters and settings could hereafter be optimized either manually
or by performing an auto tune.
To evaluate the merits of these methods, a method for determining As and Se using
CH3F in the SQ mode was likewise developed in a similar way as that in MS/MS mode,
with the only difference being that Q1 operates in "fully open" mode.
Furthermore, a method using He as collision gas in the MS/MS mode was also
developed, where the idea is that it is possible to remove the polyatomic interferences,
since these are larger and will thus collide more frequently with the He molecules and
thus lose their charge, dissociate and/or lose substantial amount of energy, such that it
becomes possible to discriminate against these using a potential barrier.[30] For As,
which e.g., suffers from the polyatomic interference from 40Ar35Cl+, the method was
optimized by measuring two standard solutions containing 5 μg/L As and 5 μg/L As with
1000 mg/L Cl interchangeably, at different flows and Q1 and Q2 at mass 75. It was found
that at a flow of 4 mL/min He, the interference from 40Ar35Cl+ was removed and this was
set as the optimal flow. Similarly for Se, which suffers from interference from, e.g., 40Ar37 +
Cl on 77Se+, 40Ar38Ar+ on 78Se+ and 40Ar40Ar+ on 80Se+, the method was optimized by
measuring a 5 μg/L Se standard solution and a blank solution at increasing He flow rate
and setting Q1 and Q2 at mass 78. At a flow of 4 mL/min He, the major interference from
40
Ar38Ar+ was significantly reduced and this was chosen as the optimal flow. However,
due to the interference of 40Ar40Ar+ on 80Se+ being very pronounced, it was chosen not to
investigate if it would be possible to monitor this isotope in order to protect the detector.
All other parameters were optimized subsequently.
Additionally, a method was also developed for the determination of As using no gas
by optimizing the parameters in order to obtain the highest sensitivity. However, it is
expected that this method is not able to deal well with spectral interferences as no
mechanism to remove on-mass interferences is available. No method was developed for
Se to protect the detector, since the ArAr+ interferences are always present and in no gas
mode there is no approach to reduce these interferences.
3.2 Optimization of SF-ICP-MS protocol for the determination of As and Se In order
to further assess the performance of the method using CH3F as reaction gas, an
alternative method using SF-ICP-MS, was developed for the determination of As and Se.
The polyatomic interferences from, e.g., 40Ar35Cl+ on 75As+, 40Ar37Cl+ on 77Se+ and 40Ar38
Ar+ on 78Se+ could be resolved by using the highest resolution setting, whereas the
interference from 40Ar40Ar+ on 80Se+ could not be resolved because this interference
requires a theoretical resolution of 9688 [22], which is approaching the maximum
resolution attainable with the SF-instrument, while the intensity of the 40Ar40Ar+ signal is
much more intense than that of 80Se+.
3.3 Calibration data and limits of detection To evaluate the methods using CH3F as
reaction gas in MS/MS mode, their analytical performances were compared to that of the
other methods developed, by measuring 5 As and Se standard solutions with
concentrations ranging between 0 - 5 μg/L to obtain a calibration curve and to determine
the limits of detection (LOD) as 3 times the standard deviation of the blank divided by
the slope.[31] 10 consecutive replicate measurements were performed to determine the
7
standard deviation of the blank. Results are shown in Table V for As and in Table VI for
Se.
For As, the lowest instrumental LOD of 0.0005 μg/L was obtained using MS/MS
mode and CH3F as reaction gas. This LOD is better than those obtained via the other
methods and better than what can be found in literature using Q-ICP-MS [16], SF-ICPMS[32], Q-ICP-MS equipped with collision/reaction cell using H2/He [16] and AAS [33].
The sensitivity of this method is also of the same order of magnitude as that found when
using no gas, since the efficiency of the reaction is high, whereas the sensitivity using He
and SF-ICP-MS is very low.
Furthermore, a good LOD is also obtained for the methods using He and no gas using
MS/MS mode and CH3F using SQ mode. However, these LODs do not give an indication
of the real strength of the methods for dealing with interferences. For this reason,
simulated matrices were analyzed. Simulated matrices containing Cl (40Ar35Cl+), Nd
(150Nd2+) and Sm (150Sm2+) were investigated, as they produce on-mass interferences,
whereas Y (89Y+), Ge (70Ge19F+) and Zn (70Zn19F+) were investigated as mass-shift
interferences. The no gas method was unable to remove the interferences from Cl, Nd and
Sm, due to no mechanism being present to deal with these on-mass interferences,
whereas the He method overcame the polyatomic interference from Cl (40Ar35Cl+) by
collision and subsequent kinetic energy discrimination, but it was unable to remove the
interference from the doubly charged ions. For the SQ method, the interferences from Y
and Ge could not be resolved, since no barrier was present to hinder these ions from
entering the reaction cell. It was only the CH3F method using MS/MS mode, which could
resolve all these interferences following the principles shown in figure 1, where on-mass
interferences were removed by Q2, due to the usage of the mass-shift mode, and massshift interferences were removed by Q1.
TABLE V. Calibration data and instrumental LOD and LOQ obtained for As with ICP-MS/MS using MS/MS mode
and the gases CH3F and He, no gas, using SQ mode and the reaction gas CH3F and SF-ICP-MS.
Reaction
Q1
Q2
Sensitivitya
Intercepta
LODb
LOQb
Set-up mode
R2
-1
gas
(amu) (amu)
(L/μg)
(count s )
(μg/L)
(μg/L)
75
89
18160 ± 250
-90 ± 100
0.999994
0.0005
0.002
MS/MS
CH3F
75
75
28120 ± 73
133 ± 80
0.999992
0.0009
0.003
MS/MS
No gas
0.9999989
75
75
3914 ± 40
-11 ± 37
0.002
0.006
MS/MS
He
SQ
CH3F
-
89
34710 ± 580
-20 ± 170
0.999987
0.001
0.004
Nuclide monitored
75
As
824 ± 18
13 ± 12
0.99996
0.01
0.04
SF-ICP-MS
Uncertainties are expressed as standard deviation (n=10)
b
LOD and LOQ are calculated as 3 and 10 times the standard deviation of a blank solution (0.14 M HNO3) divided by
the slope of the calibration curve, respectively, using 10 consecutive replicate measurements of the blank to obtain the
standard deviation.
a
For all Se isotopes monitored, a LOD below 0.02 μg/L was obtained, with the lowest
value (0.007 μg/L) obtained for the most abundant isotope 80Se. This LOD is better than
those obtained by the other methods and also better than what can be found in the
literature for Q-ICP-MS [16] and Q-ICP-MS equipped with a collision/reaction cell using
H2/He [16] and comparable to those obtained in literature for SF-ICP-MS by monitoring
82
Se [34]. The sensitivity of this method is, however, not very high in comparison to what
was found for As, since Se has multiple isotopes and the reaction to form SeCH2+ is less
favorable, but it was however still possible to obtain low LODs. The sensitivity that can
be obtained when using He is comparable to that obtained for CH3F and for the SQ using
8
CH3F it is better, but in both cases, the LODs are a bit higher, which for He is due to the
interference from 40Ar38Ar+ not being completely removed and higher standard deviations
on the blank, and for SF-ICP-MS a low sensitivity is again obtained, as for As.
Again, the real strength of the methods cannot be seen from the LODs, thus also for
Se, simulated matrices were analyzed in order to demonstrate that the method using CH3F
in MS/MS mode was the only method that successfully could overcome all interferences
investigated. Simulated matrices containing Cl (40Ar37Cl+), Ca + Cl (40Ca37Cl+), Sm
(154Sm2+), Gd (154,156Gd2+) were investigated as on-mass interferences, whereas Zr (91, 92,
94 +
Zr ), Mo (92, 94Mo+), Ge (72,73Ge19F+) and As (75As19F+) were investigated as mass-shift
interferences. The He method could remove the on-mass polyatomic interferences from
Cl and Ca (40Ar37Cl+ and 40Ca37Cl+), but the interference from the doubly charged ions
could not be overcome. Likewise, the SQ method was also unable to overcome all
investigated mass-shift interferences, as was also the case for As, due to no barrier being
present before the reaction cell. Again, it was only with the CH3F method using MS/MS
mode that all interferences could be overcome in a similar way to what was described for
As.
TABLE VI. Calibration data and instrumental limits of detection (LOD) and Quantification (LOQ) obtained for Se
with ICP-MS/MS using MS/MS mode and the gases CH3F and He, using SQ mode and the reaction gas CH3F and SFICP-MS.
Reaction
Q1
Q2
Sensitivitya
Intercepta
LODb
LOQb
Set-up mode
R2
gas
(amu)
(amu)
(L/μg)
(count s-1)
(μg/L)
(μg/L)
77
91
286 ± 10
3 ± 11
0.99998
0.02
0.07
MS/MS
CH3F
78
92
917 ± 20
7 ± 13
0.999986
0.009
0.03
MS/MS
CH3F
80
94
1944 ± 25
-2 ± 22
0.99997
0.007
0.02
MS/MS
CH3F
77
77
302 ± 8
0 ±13
0.99995
0.04
0.1
MS/MS
He
78
78
997 ± 22
99 ± 23
0.999991
0.06
0.2
MS/MS
He
91
728 ± 26
3146 ± 72
0.9996
0.2
0.8
SQ
CH3F
92
1945 ± 20
317 ± 43
0.9997
0.02
0.06
SQ
CH3F
94
4075 ± 30
175 ± 33
0.99997
0.01
0.04
SQ
CH3F
Nuclides monitored
77
Se
67 ± 5
2±5
0.9999
0.05
0.2
SF-ICP-MS
78
Se
223 ± 8
28 ± 17
0.9993
0.5
2
SF-ICP-MS
a
Uncertainties are expressed as standard deviation (n=10)
b
LOD and LOQ are calculated as 3 and 10 times the standard deviation of a blank solution (0.14 M HNO3) divided by
the slope of the calibration curve, respectively, using 10 consecutive replicate measurements of the blank to obtain the
standard deviation.
3.4 Results obtained for reference materials
For further validation of the methods using CH3F as reaction gas in the MS/MS mode,
the certified reference materials listed in table IV were analyzed using ICP-MS/MS,
relying on external calibration with Te as internal standard. (Table VII)
At a 95 % confidence level, no significant differences could be found between the
results obtained and the certified values, except for NRC-CNRC TORT-3. Thus the
accuracy of the methods was good. The reference material NRC-CNRC TORT-3 was
also measured with SF-ICP-MS, (n = 10), where a value of 67.8 ± 1.9 μg/g was found,
which is in good agreement with the results obtained using CH3F and the MS/MS mode
at a 95 % confidence level. Furthermore, for all experimental values, low standard
deviations were obtained, which indicates high precision and reproducibility, since the
analyses were performed on different digests and on different days. Additionally similar
9
results were obtained for all Se - isotopes investigates, which opens up possibilities for
performing isotopic analysis.
TABLE VII. Results obtained for the certified reference materials and the certified values for As and Se (n = 20)
Experimental
valuea (μg/g)
75
As
Certified
value(μg/g)
0.2434 ± 0.0063
0.21 ± 0.04
0.314 ± 0.013
0.27 ± 0.05
0.2835 ± 0.0097
0.29 ± 0.03
CRM 526 Tuna fish tissue
4.954 ± 0.068
4.8 ± 0.3
NRC-CNRC DORM-4 Fish
protein
6.686 ± 0.059
BRC 414 Plankton
'
NBS SRM 1575 Pine
needles
NBS SRM 1573 Tomato
leaves
NIST SRM 1568a Rice
flour
NBS SRM 1646 Estuarine
sediment
NIST SRM 1566a Oyster
tissue
NRC-CNRC TORT-3
Lobster Hepatopancreas
SeronormTM Trace
elements Urine Level 1,
Sero, Norway
a
b
Certified
value(μg/g)
Experimental valuea (μg/g)
77
Se
78
Se
80
Se
0.352 ± 0.039
0.353 ± 0.020
0.351 ± 0.010
0.38 ± 0.04
6.80 ± 0.64
3.647 ± 0.097
3.643 ± 0.066
3.626 ± 0.032
3.56 ± 0.34
6.90 ± 0.13
6.82 ± 0.28
1.753 ± 0.085
1.721 ± 0.046
1.771 ± 0.027
1.75 ± 0.10
10.59 ± 0.28
11.6 ± 1.3
0.638 ± 0.041
0.634 ± 0.032
0.654 ± 0.020
(0.6)a
13.79 ± 0.19
14.0 ± 1.2
2.233 ± 0.091
2.215 ± 0.055
2.224 ± 0.036
2.21 ± 0.24
66.94 ± 0.41
59.5 ± 3.8
11.03 ± 0.22
11.087 ± 0.091
11.07 ± 0.12
10.9 ± 1.0
84.71 ± 0.82b
79 ± 16b
16.98 ± 0.94b
16.36 ± 0.61b
16.88 ± 0.28b
13.9 ± 2.8b
Non-certified concentration of constituent element
Unit of reference material, (μg/L), since it is not a solid
4. Conclusion
In this project, new methods for an interference-free determination of As and Se at ultratrace levels using ICP-MS/MS and CH3F as reaction gas were successfully developed,
optimized and validated. This was feasible due to the possibility to perform a product ion
scan with the ICP-MS/MS technique, which made it possible to easily identify reaction
products. Low LODs could be obtained for both As and Se, and the methods match or, in
the case for As, even exceed the SF-ICP-MS technique with respect to sensitivity and
LOD, while for Se, all isotopes could be measured, while 80Se cannot be measured with
SF-ICP-MS. For Se, at least three isotopes 77,78,80Se could be measured interference-free,
which opens up possibilities for isotopic analysis. Furthermore, both methods were able
to remove interferences that other methods typically suffer from and, as a proof of
concept, it was shown that the methods were able to successfully determine As and Se in
diverse certified reference materials with high accuracy and precision.
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12
Interferentievrije bepaling van ultra-spoor niveaus van arseen en selenium
via gebruik van methylfluoride als reactiegas in ICP-MS/MS
Arseen (As) is een toxisch element; selenium (Se) is essentieel voor de menselijke gezondheid, maar
de range van optimale inname is nauw. Bepaling van beide elementen in o.m. lichaamsvloeistoffen
en in voedingsmiddelen en in de context van milieustudies is zeer relevant. Beide elementen komen
typisch in zeer lage concentraties voor en hun bepaling via ICP-massaspectrometrie (ICP-MS) is
gehinderd door het voorkomen van spectrale interferenties. In dit onderzoeksproject werd een
nieuwe methode ontwikkeld voor de bepaling van As en Se via ICP – tandem massaspectrometrie
(ICP-MS/MS).
ICP-MS/MS is een recent ontwikkelde variante van ICP-MS, waarbij een botsings-/reactiecel is
geplaatst tussen twee quadrupoolfilters. Door middel van massaselectie via de eerste
quadrupoolfilter (Q1), worden bij MS/MS alleen de doelnuclide en eventuele andere (storende)
ionen met dezelfde nominale verhouding van massa tot lading tot de botsings-/reactiecel toegelaten.
Selectieve ion/molecule reacties kunnen bijgevolg onder gecontroleerde omstandigheden in de cel
doorgaan en via scannen van het volledige massabereik met de tweede quadrupoolfilter (Q2) kunnen
de optredende reacties worden ontrafeld. Deze omstandigheden laten gebruik van reactieve gassen
toe. In dit werk werd geopteerd voor een reactiegas dat tot nog toe nauwelijks werd onderzocht in
deze context: methylfluoride (CH3F).
Voor het mono-isotopische As werd geopteerd voor interferentievrije monitoring van AsCH2+,
gevormd door reactie tussen As+ en CH3F, gevolgd door HF-eliminatie. Een analoge reactie voor Se,
laat toe 77Se, 78Se en 80Se interferentievrij te meten, wat de mogelijkheid tot isotopenanalyse opent.
Voor As werd met een waarde < 1 ng/L de laagste detectielimiet ooit opgemeten. Voor Se was de
waarde ongeveer 10 maal hoger (< 10 ng/L), maar deze waarde is nog steeds competitief met de
state-of-art waarde geboden door dubbel-focusserende sector-veld ICP-MS.
De superieure mogelijkheden tot het vermijden van spectrale interferenties van de ontwikkelde
methode werden geïllustreerd via gebruik van synthetische matrices die met verschillende methodes
werden geanalyseerd. Ten slotte werd de ontwikkelde methode gevalideerd door succesvolle analyse
(As- en Se-bepaling) van een grote reeks gecertificeerde referentiematerialen. Hiervoor werd
gesteund op externe kalibratie met Te als inwendige standaard.