175
J.M. Ringer, Eur. J. Mass Spectrom. 19, 175–185 (2013)
Received: 19 April 2011 n Revised: 19 March 2013 n Accepted: 19 March 2013 n Publication: 18 July 2013
EUROPEAN
JOURNAL
OF
MASS
SPECTROMETRY
Detection of nerve agents using proton
transfer reaction mass spectrometry with
ammonia as reagent gas
Joachim M. Ringer
Wehrwissenschaftliches Institut für Schutztechnologien–ABC-Schutz, Humboldsttraße 100, D-29633 Munster, Germany.
E-mail: [email protected]
The chemical warfare agents (CWA) Sarin, Soman, Cyclosarin and Tabun were characterised by proton transfer mass spectrometry
(PTRMS). It was found that PTRMS is a suitable technique to detect nerve agents highly sensitively, highly selectively and in near realtime. Methods were found to suppress molecule fragmentation which is significant under PTRMS hollow cathode ionisation conditions.
In this context, the drift voltage (as one of the most important system parameters) was varied and ammonia was introduced as an
additional chemical reagent gas. Auxiliary chemicals such as ammonia affect ionisation processes and are quite common in context
with detectors for CWAs based on ion mobility spectrometry (IMS). With both, variation of drift voltage and ammonia as the reagent
gas, fragmentation can be suppressed effectively. Suppression of fragmentation is crucial particularly concerning the implementation
of an algorithm for automated agent identification in field applications. On the other hand, appearance of particular fragments might
deliver additional information. Degradation and rearrangement products of nerve agents are not distinctive for the particular agent but
for the chemical class they belong to. It was found that switching between ammonia doped and ordinary water ionisation chemistry can
easily be performed within a few seconds. Making use of this effect it is possible to switch between fragment and molecular ion peak
spectra. Thus, targeted fragmentation can be used to confirm identification based only on single peak detection. PTRMS turned out to
be a promising technique for future CWA detectors. In terms of sensitivity, response time and selectivity (or confidence of identification,
respectively) PTRMS performs as a bridging technique between IMS and GC-MS.
Keywords: PTRMS, proton transfer reaction, CWA, chemical warfare agent, Sarin, Soman, Cyclosarin, Tabun, chemical detection
Introduction
More than ever, hazardous chemicals released intentionally
or by accident pose a significant threat to public life all over
the world. The range of relevant chemicals and chemical
classes in this context is much more comprehensive than
it has ever been before. Regardless o f the fact that the
Cold War period ended 20 years ago, chemical warfare
agents (CWA) are still attractive for terrorists due to their
high toxicity and disastrous impact on casualties. Currently,
analytical techniques such as ion mobility spectrometry
(IMS) or flame photometry are made use of to design
ISSN: 1469-0667 doi: 10.1255/ejms.1222 hand-held CWA detectors and warning equipment in order
to enable acting personnel to take measures of personal
and collective protection in case of the appearance of CWA.
Both techniques, however, do not meet asymmetric threat
scenario requirements comprehensively and possibilities of
technical improvement are limited due to physical regularities. In contrast, classical gas chromatography-mass spectrometry (GC-MS) is a powerful mass selective tool but not
suitable to put hand-held chemical detectors into practice
and to detect chemical hazards in near real time.1,2
© IM Publications LLP 2013
All rights reserved
176
Detection of Nerve Agents using PTRMS with Ammonia as the Reagent Gas
Innovative analytical approaches and techniques are
­atmosphere and is diluted by an adjustable airstream passing
required to bridge the analytical gap between hand-held
the polyethylene permeation tube in a closed system.
detector techniques such as IMS and steady techniques such
Basically, the permeation rate (or the absolute amount per
as GC-MS in terms of fast (near real time) detection, high
time unit, respectively) is temperature controlled but also
sensitivity and high selectivity or information content respec- depends on the agent properties as well as on the tube
tively. Proton transfer reaction mass spectrometry (PTRMS)
features. Thus, concentration is controlled by temperature
has been considered as an appropriate technique to fill the
on the one hand and flow rate of the dilution air stream on
gap and successfully fulfil the requirements mentioned
the other. Considering a PTRMS sample flow rate up to
before.
1 L min–1, the generator flow rate varied between 1,5–2 L min–1
Organophosphorous nerve agents such as Sarin used at
depending on the target concentration or the corresponding
Tokyo underground in 1991 belong to the most hazardous
adjustments, respectively.
agents and require the most demanding detection features.
The main objective of the experiments was not to figure
Therefore, this work focuses on Sarin and Tabun-type
out detection limits of PTRMS technique in general because
­phosponic and posphoric acid esters.
PTRMS
alreadyformation
well ofknown
forgasitsadduct
high
sensitivity
and
essential
in respectis
of suppressing
higher reagent
ions (or
reactant ions, respectively),
+
(H2O)near
product ions (protonated
VOCs and fragment
ions if present)
are then sampled
an orifice at
nH . The real-time
detection.
Instead,
the purpose
of through
the investhe end of the drift tube and fo- cused, via a specially designed transfer lens system, into the mass spectrometer
detector.
The PTRMS
high sensitivity
on a classical
quadrupole mass filter detector.
In case of PTR-ToF
tigation
was
to getis based
a deeper
understanding
of ionisation
8000 ( m/z) ratios of the ions are determined from the measured fight times [6-7].
mechanisms,
reactions
and
molecular
rearrangements
of
To conduct the experiments the PTRMS systems were challenged with test gases with a defined agent
concentration. The test gases were produced by special gas generators based on permeation techniques and
nerve
agents
under
PTRMS
ionisation
conditions.
Therefore,
suitable to vaporize highly super toxic chemicals. The target compounds were sealed in polyethylene plastic tubes.
The small amount of agent permeating through the tubes wall evaporates to the atmosphere and is diluted by an
medium
concentrations in the lower three-digit ppbv range
PTRMS techniques and, in particular, the hardware manu- adjustable
airstream passing the polyethylene permeation tube in a closed system. Basically, permeation rate (or
absolute
amount
per time
respectively)
is temperature controlled but in
alsoorder
depends to
on the
agent
were
chosen
forunitthe
individual
experiments
ensure
factured by Ionicon Analytic GmbH is described in a variety of the
properties as well as on the tube fea- tures. Thus, concentration is controlled by temperature on the one hand and
flow adequate
rate of the dilution
air stream
on the other
Considering
a PTRMS sample
flow ratesensitivity
up to 1 l/min the
agent
signal
in hand.
PTRMS
spectra.
The high
publications.3–5
generator flow rate varied between 1,5-2 l/min depending on the target con- centration or the corresponding
of PTRMS
was challenged with concentrations of 200 ppbv,
H3O+ reactant ions are produced from water vapour intro- adjustments
respectively.
Main objective of the experiments was not to figure out detection limits of PTRMS technology in general because
duced as a reagent gas into a hollow cathode from a water PTRMS
foris already
the PTR-ToF,
concentrations
varying
between
500 ppb
well known for the
high sensitivity
and near real-time
detection. Instead,
the purpose
of the
investigation was to get a deeper under- standing of ionisation mechanisms, reactions and molecular
liquid sample holder via a mass flow controller. These reactant rearrangements
and 1.000 ppb
depending
on
the
agent.
GC-FPD
techniques
of nerve agents under PTRMS ionisation conditions. Therefore, medium concentrations in the
three-digit ppbv range were chosen for the individual experiments in order to en- sure adequate agent
ions, under the influence of a voltage gradient, pass through lower
were
made use of to check and confirm an adjusted agent
signal in PTRMS spectra. The PTRMS high sensitive was challenged with concentrations of 200 ppbv, for the
the concentrations varied be- tween 500 and 1.000ppb depending on the agent. GC-FPD techniques were
a small orifice into an adjacent drift tube section, where the PTR-ToF
­concentration.
made use of to check and confirm an adjusted agent concentration.
analyte is introduced (via a gas inlet system with an adjustable
Tabun (GA)
Sarin (GB)
Soman (GD)
Cyclosarin (GF)
flow between 50 ssc and 1000 ssc and an adjustable temperature of between 40°C and 150°C). The operating pressure in the
O
O
O
O
drift tube is usually maintained between 2.2–2.4 mbar while the
EtO P CN
F P
F P
F P CH3
drift tube voltage and temperature can be varied between 400 V
CH3 O
CH3 O
O
N
and 1000 V and 40°C and 120°C, respectively.
t-Bu
Within the drift tube, proton transfer reactions occur
m/z 162
m/z 140
m/z 182
m/z 180
between reactant ions and any volatile organic compounds
(VOCs) present in the sample with proton affinities greater
Tabun (NATO
belongs GA)
to the
group oftoorganophosphates
than that of the reagent gas. The drift voltage has a significant Basically,
Basically,
Tabunacronym
(NATOGA)
acronym
belongs
the group
Sarin,
Soman
and
Cyclosarin
(NATO
acronyms
GB,
GF) signify the
influence on fragmentation of product ions, resulting from the whereas
of organophosphates whereas Sarin, Soman GD
andandCyclosarin
of organophosponates.
Chemically
the lastthe
mentioned
differ
each
reaction of reactant ions with any VOCs via dissociative and chemical
(NATOclass
acronyms
GB, GD and
GF) signify
chemical from
class
in respect of the side group
which is isopropyl
in case
of Sarin,
non-dissociative proton transfer and proton transfer in the other
of only
organophosponates.
Chemically,
the latter
differ
frompinacolyl
each in
of Soman
cyclohexyl of
in case
of Cyclosarin.
drift tube. Further on, drift voltage is essential in respect of case
other
onlyand
in respect
the side
group which is isopropyl in the
similarities the
of theof
phosphoric
acid in
differ
suppressing formation of higher reagent gas adduct ions (or Regardless
case ofstructural
Sarin, pinacolyl
in esters
the case
Somanand
andphosphonic
cyclohexyl
in terms
of physical properties, chemical stability and toxicity.
reactant ions, respectively), (H2O)nH+. The product ions (proto- significantly
the case
of Cyclosarin.
Regardless of structural similarities, the esters of the
nated VOCs and fragment ions if present) are then sampled
phosphoric and phosphonic acids differ significantly in terms
through an orifice at the end of the drift tube and focused, via
a specially designed transfer lens system, into the mass spec- of physical properties, chemical stability and toxicity.
trometer detector. The high sensitivity of the PTRMS is based
2
on a classical quadrupole mass filter detector. In the case of
PTR-ToF 8000 (m/z), ratios of the ions are determined from the
measured fight times.6,7
To conduct the experiments the PTRMS systems were
Proton transfer from a reactant ion H3O+ to an analyte A (for
challenged with test gases with a defined agent concentra- example, CWA) follows the basic equation:
tion. The test gases were produced by special gas generators
H3O+ + A ® [A.H]+ + H2O
based on permeation techniques and suitable for vaporise
highly super toxic chemicals. The target compounds were
However, depending on the chemical and physical propersealed in polyethylene plastic tubes. The small amount of
ties of the analytes, reagent gas adducts of the product might
emerge:
agent permeating through the tube wall evaporates into the
Experimental
Results
J.M. Ringer, Eur. J. Mass Spectrom. 19, 175–185 (2013)177
initially in the hollow cathode. As soon as the reactant ions
approached the ammonia-enriched sample air stream in the
drift tube, presumably the ammonia-based reactant ions were
formed in a very fast proton transfer process (due to their high
proton affinity) which subsequently reacted with the analyte to
produce ions.
Figures 1(a)–(e) show the PTR mass spectra of Sarin at
different drift voltages. The spectra were recorded with an
unmodified highly sensitive PTRMS instrument from Ionicon
Analytik GmbH. No additional reagent gas was added and the
system was operated at pure water chemistry. The spectra were
H3O+ + A + nH2O ® [A.H.(H2O)n ]+ + H2O
In the context of CWA measurements, adducts up to n = 2
were obtained in significant amounts. Both analyte properties
and drift voltage have a significant influence on the appearance of the different product ion species and adducts.
Further on, in the context of this work, ammonia was used as
an additional reagent gas to suppress molecule ­fragmentation.
As ammonia was not added instead of but additional to water
and not directly to the hollow cathode but together with the
analyte gas stream, water-based reactant ions were formed
(b): 500V
45
40
40
35
35
30
30
3
45
25
cps x 10
cps x 10
3
(a): 600V
20
25
20
15
15
10
10
5
5
0
0
80
100
120
140
m/z
160
180
200
80
100
120
140
m/z
160
180
200
100
120
140
m/z
160
180
200
(d): 300V
(c): 400V
45
30
40
25
35
4
20
25
cps x 10
cps x 10
3
30
20
15
15
10
10
5
5
0
0
80
100
120
140
m/z
160
180
200
100
120
140
m/z
160
180
200
80
(e): 200V
30
25
cps x 10
4
20
15
10
5
0
80
Figures 1(a)–(e). PTR-Quad-MS spectra of nerve agent Sarin (GB). The spectra were recorded at different drift voltages. No a
­ dditional
reagent gas was used. Therefore, gas-phase ion chemistry is just water based. There is a significant impact of the drift voltage on
fragmentation behaviour of the target compound.
6
178
Detection of Nerve Agents using PTRMS with Ammonia as the Reagent Gas
recorded with a dwell time of 100 ms. The drift tube pressure
Further on, in experiments with simulants, a peak at m/z
was 2.1 mbar and the drift tube temperature was 60°C.
97 corresponding to protonated methylphosphonic acid
At a drift voltage of 600 V no molecular peak is detectable, predominates the spectra instead of m / z 99 which appears
as shown in Figure 1(a). A peak at m/z 99 is most significant
in experiments with real nerve agents and corresponds to
and another peak at m/z 97 is detectable. The m/z 97 corre- protonated fluoro-methylphosphonic acid.
Figure 1(a)-(e): PTR-Quad-MS spectra of nerve agent Sarin (GB). The spectra were recorded at different drift
methylphosphonic
acid
as water
a Sarin
voltages. No sponds
addi- tional with
reagentthe
gas protonated
was used. Therefore,
gas phase ion chemistry
is just
based. There The fragmentation behaviour of Sarin was confirmed by
is a significant impact of the drift voltage on fragmentation behaviour of the target compound.
investigations with chemically related agents and gave reason
hydrolysis
and
rearrangement
product
whereas
the
m/z 99
At a drift voltage of 600V no molecular peak is detectable as shown in fig. 1(a). A peak at m/z 99 is most
significant, another
peak at m/z to
97 is
detectable. The m/z 97 corre- sponds and
with the
protonated
methylto consider further means to manipulate gas-phase ion chemcorresponds
fluoroorganophosphonates
is well known
phosphonic acid as a Sarin hydrolysis and rear- rangement product whereas the m/z 99 corresponds to fluorofrom
classical
EI
mass
spectra.
istry
of nerve agents in PTRMS. The variation of drift voltage
organophosphonates and is well known from classical EI mass spectra.
affected the kinetic energy ions which can gain between two
protonated
protonated
collisions with atmospheric drift tube compounds. Another
approach was to reduce the mean free path between two collimethyl-phosphonic acid
fluoro-methylphosphonic acid
sions
by increasing the drift tube pressure. It turned out quite
H
H
O
O
soon
that
variations of this parameter, at least in the range
+
HO P+ OH
F P OH
made possible by the equipment manufacturer, does not affect
fragmentation behaviour significantly in the case of nerve
CH3
CH3
agents. Finally, ammonia was considered as the reagent gas to
m/z 97
m/z 99
affect gas-phase ion chemistry. Ammonia is quite a common
reagent gas for use with IMS because for many reasons but
not primarily to suppress fragmentation.1,2
Thus, both peaks correspond to organophosphonate
Thus, both peaks correspond to organo-phosphonate fragments. Decreasing the drift
fragments. By decreasing the drift voltage to 500 V but
Figures 2(a)–(e) s h o w t h e mass spectra of Sarin at
voltage to 500V but keeping the agent concentration constant the intensity of m/z 99
keeping the agent concentration constant, the intensity of
different drift voltages. The spectra were recorded with the
increases. This is shown in fig. 1(b). At extremely weak m/z 141 corresponding to prosame instrument and the same system adjustments. The
m / z 99 increases. This is shown in Figure 1(b). At extremely
tonated Sarin
canmbe
observed
in
this
spectrum.
only difference was that ammonia was added.
weak
/ z 141 corresponding to protonated Sarin can be
observed in this spectrum.
An approach to replace the water reservoir of a PTRMS
Decreasing Decreasing
the drift voltage
400Vvoltage
the m/zto
99400 V,
continues
whereas
the
m/z
thetodrift
the increasing
system
by an
ammonia
source
m / z An
99approach
continues
was by
discarded
at source
a verywas
early
to replace the water
reservoir
of a PTRMS
system
an ammonia
discarded at a very
increasing,
whereas
the
stage.
It
also
turned
out
it isto not
stringently
required
m / z 97 vanishes
completely,
97 vanishes almost completely as demonstrated
in fig. 1(c).almost
Coincidently,
a peak
at turned
m/z out that it is not stringentlythat
early
stage.
It also
required
add gaseous
ammonia
from a cylinder to the
flow air steam
a concentrated
aqueousair
solution of ammon
air
Instead,
a low
to addbubbling
as demonstrated
inappears.
Figure A1(c).
a analyte
peak
at +stream.
m/z
gaseous
ammonia
fromthrough
a cylinder
to the analyte
117, the water
adduct of m/z 99
peakCoincidently,
of protonated Sarin
[GB.H]
at m/z 141
(25% by volume) and adding this ammonia enriched air stream to the sample airstream produced by the test
stream.
Instead,
bubbling
a
low
117, detectable.
the water adduct of m/z 99, appears. A peak
of protoflow air steam through a
is now clearly
generator was proved successful and easy to put into practice. A flow rate of 50ml/min through the aqueous
+
nated
Sarin300V
[GB.H]
concentrated
aqueous
solution
ammonia
(25%
by volume)
at m/z
141
is now
clearly
rate between
20-100ml
did not deliver significa
ammonia
was chosen whereby
variation
of theofflow
In the range
between
and 400V
drift
voltage
meets
point detectable.
at solution
which theofm/z
99, the
differentmeets
results.
In
the
range
between
300 V
and
400 V
drift
voltage
and
adding
this
ammoniaenriched
air
stream
to
the
sample
m/z 117 and the m/z 141 appear with almost the same intensity (fig. 1(d)). Even a small
at the point at which the m/z 99, the m/z 117 and the m/z 141
m/z 159 corresponding to the protonated Sarin/water adduct [GB.H2O.H]+ is visible.
appear with almost the same intensity [Figure 1(d)]. Even
Exceeding this point and decreasing the voltage down to 200V makes the m/z 99 disTest Gas
a small m/z 159 corresponding to the protonated Sarin/
appear almost completely what is shown
in fig 1(e). The most intense peaks of the
Generator
water adduct [GB.H 2O.H] + is visible. Exceeding this point
spectrum now correspond to the protonated Sarin at m/z 141 followed by its water adand decreasing the voltage down to 200 V makes the m/z 99
PTR
duct at m/z
159.
disappear
almost completely, as shown in Figure 1(e). The
most intense peaks of the spectrum now correspond to the
Air
MFC
protonated Sarin at m/z 141 followed by its water adduct at
m/z 159.
Regardless o f the type ion species, drift voltages of
around 400 V deliver the largest
total amount of ions to
3
the mass spectrometry detector. However, fragmentation
Aquous soulution
predominates at this voltage. In order to avoid fragmentation,
of ammonia
drift voltages lower than 400 V are required under ordinary
ionisation conditions based on water reactant ions.
The results obtained so far with real CWA are consistent
with results from of PTRMS experiments with simulants
such as diisopropyl-methylphosphonate (DIMP) published in
the literature.7 Fragmentation can be suppressed efficiently
by reducing the drift voltage. However, the disadvantage of
low drift voltages is that the higher reactant ion clusters
Figure 2. Experimental setup for ammonia feeding of the
[H.(H2O)n]+ with n up to 4 appear in what impairs the estianalyte air stream from the test gas generator. The gas flow
mation of analyte concentration with models developed
by
Fig. 2: experimental
setup for ammonia feeding of the analyte air stream from the te
through the bubbler was controlled by a mass flow controller
Ionicon and based on the intensity of m/z 19 (protonated
(MFC).
gas generator. The
gas flow through the bubbler was controlled by a mass flow contr
water).3
ler (MFC).
Regarding comparability of ammonia and non-ammonia experiments or to avoid diluti
J.M. Ringer, Eur. J. Mass Spectrom. 19, 175–185 (2013)179
airstream produced by the test gas generator proved t o
b e successful and easy to put into practice. A flow rate
of 50 mL min–1 through the aqueous solution of ammonia
was chosen whereby a variation in the flow rate between
20–100 mL did not deliver significantly different results.
Regarding comparability of ammonia and non-ammonia
experiments or to avoid dilution effects by the ammoniaenriched air stream, respectively, an appropriate stream of
clean dry air was added to the test gas in the non-ammonia
experiments.
(a) 600 V
(b) 500 V
30
25
25
20
20
cps x 10
3
30
3
cps x 10
As expected, ammonia effects ionisation in PTRMS
­significantly. Starting again with a drift voltage of 600 V,
hardly any fragmentation can be observed. Primarily,
ion species containing unfragmented Sarin are formed
whereas the protonated Sarin/ammonia cluster [GB.NH3.H]+
­predominates at m/z 158, even at a drift voltage of 600 V, as
demonstrated in Figure 3(a).
Decreasing the voltage step by step to 400 V does not
affect fragmentation or appearance of different ion species
considerably. Most remarkable is that at 400 V drift voltage a
15
10
10
5
5
0
0
80
100
120
140
m/z
160
180
200
(c) 400V
80
100
120
140
m/z
160
180
200
100
120
140
m/z
160
180
200
(d) 300V
30
25
25
20
20
cps x 10
3
30
3
cps x 10
15
15
15
10
10
5
5
0
0
80
100
120
140
m/z
160
180
200
100
120
140
m/z
160
180
200
80
(e) 200V
30
25
cps x 10
3
20
15
10
5
0
80
Figures 3(a)–(e). PTR-Quad-MS spectra of nerve agent Sarin (GB). The spectra were recorded at different drift voltages. Ammonia
was used as an additional reagent. Compared to water-based gas-phase ion chemistry, fragmentation of the target compounds is
­suppressed significantly at any drift voltage.
10
180
Detection of Nerve Agents using PTRMS with Ammonia as the Reagent Gas
An approach to replace the water reservoir of a PTRMS system by an ammonia source was discarded at a very
early stage. It also turned out that it is not stringently required to add gaseous ammonia from a cylinder to the
analyte air stream. Instead, bubbling a low flow air steam through a concentrated aqueous solution of ammonia
+
peak at
/ z 175 corresponding
to ammonia
[GB.(NH3)2.H]
is clearly
[Figureto5(a)].
Remarkably,
even protonated
unfragmented)
(25%
by mvolume)
and adding this
enriched
air stream
the sample
airstream
produced (­by
the test gas
visible.
As
in
t
h
e
case
of
pure
water
chemistry,
the
total
Sarin
as
well
as
its
water
clusters
at
m
/
z
159
and m / z
generator was proved successful and easy to put into practice. A flow rate of 50ml/min +through the aqueous
amount of ions produced and delivered to the MS detector 177, corresponding to [GB.H2O.H] and [GB.(H2O)2,H]+, ­can be
solution of ammonia was chosen whereby variation of the flow rate between 20-100ml did not deliver significant
seen. Varying the drift voltage attains the same effect as in
meets a maximum around this particular voltage. A reduction
different results.
t h e case of PTR-Quad-MS, namely the suppression of Sarin
of the drift voltage to 200 V is associated with a decrease of
both
the
fragmentation,
asfrom
shown
intest
Figures
/ z 141 and the
m / for
z 158
intensity,
whereas
the analyte
Using
Figure 2. m
Experimental
setup
ammonia
feeding
of the
air stream
the
gas 5(b)–(c).
generator.
Theammonia
gas flow
as
a
dopant
does
effectively
suppress
fragmentation o f all
m/z 175 intensity
increases
slightly, as by
shown
in Figure
3(e).
through
the bubbler
was controlled
a mass
flow controller (MFC).
voltages investigated.
Protonated
Sarin only
appears
at high
Regardless
o f the drift voltage,
fragmentation
did not play experiments
Regarding
comparability
of ammonia
and non-ammonia
or to avoid
dilution effects
by the
ammonia
voltages
with
a
very
weak
peak
at
a
significant
role
in
t
h
e
presence
of
In any
case, of clean dry air was added to the testm
/ z in
141
enriched air stream respectively anammonia.
appropriate
stream
gas
the[Figure
non- 5(d)].
fragmentation
can
be
suppressed
efficiently
using
ammonia
Reducing
the
drift
voltage,
this
peak
disappears.
The peaks
ammonia experiments.
as a reagent gas.
corresponding to the single and the double ammonia clusAs expected ammonia effects ionisation in PTRMS significantly. Starting again with a drift voltage of 600V
tered Sarin at m / z 158 and m / z 175 are t h e most signifiFurther experiments were carried out with a PTR-ToF 8000
hardly any fragmentation can be observed. Primarily ion species containing un-fragmented Sarin are formed
cant
in all ammonia chemistry spectra, as demonstrated
instrument from Ionicon Analytik GmbH. The objective was
+
whereas
the comparability
protonated Sarin/ammonia
cluster
Figures 5(d)–(f).at m/z 158 even at a drift voltage of
to figure out
of quadrupole and
ToF [GB.NH
detector3.H]in predominates
600V
as demon- strated in fig. 3(a).
This is different to PTR-Quad-MS, where just the single
results.
ammonia
clustered or
Sarin
is dominant
Figures
5(a)–(f)
depict
PTR-ToF-MS
spectra
of
Sarin.
As
m/z 158ion
and any
Decreasing the voltage step by step to 400V does not affect fragmentation
appearance ofatdifferent
in
case
of
the
experiments
with
the
drift
voltage
at
highly is
sensitive
m/z
wellcorresponding
as m/z 175 playtoa minor role
species considerably. Most remarkable
that atPTRMS
400V drift voltage a peak
at 141
m/zas175
i n s t r u m e n t , +the spectra were recorded at different drift
[Figure 3(a)–(d)]
[GB.(NH3)2.H] is clearly visible. As in case of pure water chemistry, the total amount of ions produced and
voltages. The experiments were conducted with both pure
Another interesting difference to PTR-Quad-MS operated
delivered to the MS detector meets a maximum around this particular voltage. A reduction of the drift voltage to
water and ammonia gas- phase ion chemistry. In this paper, at ammonia chemistry is the appearance of significant peaks
the 159
m/zand
158m/z
intensity,
whereas
the m/z
175 intensity
200V
is associated
with
a decrease
ofare
both,
the m/z 141 and
at m/z
however,
only the most
revealing
spectra
presented.
176 next
to the main
ammonia
cluster
increases
slightly
as shown in fig.behaviour
3(e).
Basically,
the fragmentation
of Sarin in
peaks. Considering the intensity of both peaks it is unlikely
Regardless
drift voltagetofragmentation
not play
role
in presence
of ammonia.
In any
case
PTR-ToF-MSthe
is comparable
PTRQuad-MS. did
Product
ion a significant
that they only
arise
from 13C isotopes.
Therefore,
they
seem
fragmentation
can be suppressed
efficiently
ammonia
reagent
gas.single water cluster [GB.H O.H]+ at m/z
species of fragmented
and unfragmented
Sarinusing
appear
in
to as
be arelated
to the
2
changing proportions, depending on t h e drift voltage and
159 and the mixed ammonia/water cluster [GB.H2O.NH3.H]+
t h e type of reagent gas. However, in PTR-ToF-MS, reagent
at m/z 176.
gas adducts of Sarin and its fragments are much more
There are further differences between PTR-Quad-MS
distinct than in PTR-Quad-MS. Whereas protonated fluoro- and PTR-ToF-MS spectra recorded under the same experimental conditions although PTR hardware in both systems is
methylphosphonate at m/z 99 is the only significant peak in
PTR-Quad-MS, at 600 V drift voltage and pure water chem- identical according the manufacturers information.
istry the equilibrium is shifted to the single or even the double
Regardless of the type of reagent gas, nerve agents show a
significantly different proportional distribution of p
­ rotonated
water clustered adducts at m/z 117 and 135, respectively
(a) water chemistry
+
[FMP.H]
+
[FMP.H O.H]
4
+
40
Intensity [x10 cps]
[GB.H]
+
[GB.H O.H]
30
+
[GB.H]
2
3
2
3
Intensity [x10 cps]
(b) ammonia chemistry
20
10
[GB.NH 3.H]
+
+
[GB.(NH ) .H]
3 2
30
20
10
0
200
300
400
Drift Voltage [V]
500
600
0
200
300
400
500
600
Drift Voltage [V]
Figures 4. Different ion species in the measurement of Sarin with PTR-Quad-MS and process of peak intensities at (a) water and (b)
ammonia gas-phase ion chemistry depending on the drift voltage. Fragmentation products predominate in the case of water chemistry
at higher
drift voltages.
In the case ion
of ammonia,
chemistry
is suppressed
any drift
voltage and the
Fig.
4(a)-(b):
different
species
in fragmentation
measurements
of almost
Sarinc­ ompletely
(GB) atwith
PTR-Quad-MS
single ammonia adduct of Sarin is formed primarily.
and process of peak intensities at water (a) and ammonia (b) gas phase ion chemistry
11
J.M. Ringer, Eur. J. Mass Spectrom. 19, 175–185 (2013)181
produced in the same proportional distribution. Nevertheless,
spectra of both systems differ from each other. This is an indication that significant amounts of some ion cluster speci­es get
lost either ­overcoming the interface to the mass ­spectrometer
species and their related reagent gas adduct clusters (single-,
double- and mixed clustered), as shown in Figures 2(a)–(d)
compared to Figures 4(d)–(f). Assuming that the PTR hardware
in both systems is identical, indeed the same ion species are
(a) 600 V, water chemistry
(d) 600 V, ammonia chemistry
900
900
800
800
700
700
600
600
cps
1000
cps
1000
500
400
300
300
200
200
100
100
0
80
100
120
m/z
140
160
0
180
(b) 400 V, water chemistry
800
800
700
700
600
600
cps
900
cps
1000
900
500
400
300
300
200
200
100
100
100
120
m/z
140
160
0
180
(c) 200 V, water chemistry
900
800
800
700
700
600
600
cps
1000
900
500
400
300
300
200
200
100
100
100
120
m/z
140
m/z
140
160
180
80
100
120
m/z
140
160
180
160
180
500
400
80
120
(f) 200 V, ammonia chemistry
1000
0
100
500
400
80
80
(e) 400 V, ammonia chemistry
1000
0
cps
500
400
160
0
180
80
100
120
m/z
140
Figures 5. PTR-ToF-MS spectra of nerve agent Sarin (GB) at water (a)–(c) and ammonia (d)–(f) gas-phase ion chemistry (sequence
of the spectra in vertical depiction). As in case of PTR-Quad-MS the spectra were recorded at different drift voltages.
5
182
Detection of Nerve Agents using PTRMS with Ammonia as the Reagent Gas
or in mass spectrometer itself. At least they do not reach
the detector plate. Therefore, proportional distribution of
ions appearing in the spectra seems to be dependent on the
stability of the particular type of ion species, the PTR-MS
interface, possibly the type mass spectrometer and, in general,
of course, on the PTR ionisation which should be identical in
this case, as mentioned before.
On the other hand, water chemistry fragmentation seems to
take place, to a higher extent, in the PTR-Quad-MS compared
to the ToF system. A significant higher amount of unfragmented nerve agent can be detected with PTR-ToF-MS under
the same experimental conditions as shown in Figures 1(a)–(d)
compared to Figures 4(a)–(c). If the PTR hardware was exactly
identical in both systems, the appearing ion species, their
proportional distribution and fragmentation behaviour should
be identical as well. Certain differences in the PTR hardware
and/or different interactions of the PTR hardware with the
mass spectrometer interface are the only explanation for this
phenomenon.
Cyclosarin (GF) and Soman (GD) can be considered as Sarin
derivatives and differ only in respect of their side groups.
Both compounds were investigated with PTR-ToF-MS in
the same way as Sarin but not all spectra are depicted in
this work because similarities with regard to fragmentation
behaviour under PTR ionisation conditions are obvious.
As shown in Figures 7(a)–(c), Cyclosarin behaves completely
analogously to Sarin. Again, in the case of water chemistry
and a drift voltage of 600 V, intense peaks appear at m/z 117
and m/z 135, corresponding to the fragment/water clusters
discussed before [ Figure 7(a)]. Protonated Cyclosarin and
its single water adduct appear with almost the same peak
intensity at this drift voltage.
Decreasing the voltage but keeping water chemistry leads
to almost complete suppression of fragmentation as in the
(a) water chemistry
case of Sarin. Figure 7(b) shows the spectrum recorded at
200 V drift voltage. Remarkably, under these conditions, the
water clustered ion species are preferably formed compared
to the just protonated species. This is applicable for both
the analyte Cyclosarin and its fluoromethylphosphonate fragment.
Introducing ammonia as the reagent gas makes ion chemistry switch and leads to the same effects as in the case of
Sarin. The peaks of single- and double ammonia clustered
Cyclosarin at m/z 198 and m/z 215 predominate in the spectrum whereas unclustered Cyclosarin does not appear in
significant amounts, as shown in Figure 7(c). As with Sarin,
the water cluster and the mixed water/ammonia cluster also
appear at m/z 199 and m/z 216.
To complete the series of Sarin derivative experiments,
Soman was investigated. Selected spectra are shown in
Figures 8(a) at 600 V with water and 8(b) at 300 V with
ammonia as t h e reagent gas. In general, ionisation behaviour is comparable to Sarin and Cyclosarin under PTR
­ionisation conditions.
Obviously, due to their structural and chemical similarities, Sarin, Cyclosarin and Soman spectra turn up with the
same distinct characteristics in terms of fragmentation,
clustering and methods to suppress fragmentation via drift
voltage and the use of ammonia as the reagent gas.
In contrast to all Sarin derivatives, Tabun belongs to the
chemical class of organophosphates. Selected Tabun spectra
recorded with PTR-ToF-MS are shown in Figures 9(a)–(c).
Tabun renders a more complex fragmentation behaviour
than the Sarin derivatives. The ion species shown in Figure
9(a) are either directly related to Tabun (m/z 163 and m/z
181) or can be traced back to fragments and rearrangement
products. For example, there is a set of peaks at m/z 135 and
m/z 153. This is due to a rearrangement product in which the
(b) ammonia chemistry
1000
1000
+
+
[FMP.H]
+
[FMP.H2O.H]
900
[GB.H]
+
[GB.H2O.H]
+
800
[FMP.(H2O)2.H]
900
+
800
[GB.(H2O)2.H]
700
Intensity [cps]
Intensity [cps]
700
600
500
400
600
500
400
+
300
300
[GB.H]
+
[GB.NH3.H]
200
200
[GB.(NH3)2.H]
100
100
+
0
0
200
300
400
Drift Voltage [V]
500
600
200
300
400
Drift Voltage [V]
500
600
Figures 6(a)–(b). Different ion species in measurements of Sarin with PTR-ToF-MS and process of peak intensities at (a) water
and (b) ammonia gas- phase ion chemistry depending on the drift voltage. It is obvious that ion species corresponding to reagent
gas adducts of Sarin (and its fragments in the case of water chemistry) are much more distinct in the spectra compared to PTRQuad-MS depicted in Figures 4(a)–(b).
Fig. 6(a)-(b): different ion species in measurements of Sarin (GB) with PTR-ToF-MS
and process of peak intensities at water (a) and ammonia (b) gas phase ion chemistry
depending on the drift voltage. It is obvious that ion species corresponding to reagent
gas adducts of Sarin (and its fragments in case of water chemistry) are much more dis-
J.M. Ringer, Eur. J. Mass Spectrom. 19, 175–185 (2013)183
(c) 400 V, ammonia chemistry
800
800
700
700
600
600
500
500
cps
cps
(a) 600 V, water chemistry
400
400
300
300
200
200
100
100
0
0
80
100
120
140
m/z
160
180
200
80
220
100
120
140
160
180
200
220
m/z
(b) 200 V, water chemistry
800
700
600
cps
500
Introducing
ammonia as reagent gas makes ion chemistry switch and leads to the same
400
effects as in case of Sarin. The peaks of single and double ammonia clustered Cyclo300
sarin
at m/z 198 and 215 predominate in the spectrum whereas un-clustered Cyclosarin
200
does
not appear in significant amounts as shown in fig. 7(c). Comparable to Sarin also
100
the0 water cluster and the mixed water/ammonia cluster appears at m/z 199 and 216.
80
100
120
140
m/z
160
180
200
220
Figures 7(a)–(c). PTR-ToF-MS spectra of Cyclosarin recorded at different drift voltages and with water and ammonia as reagent gases.
Generally,
is comparable
to Sarin
PTRderivative
ionisation conditions.
Tobehaviour
complete
the series
ofunder
Sarin
experiments Soman (GD) was investigated.
Selected spectra are shown in figures 8(a) at 600V with water and 8(b) at 300V with
shown
Cyclosarin
behaves
completely
analogue
Sarin.
Again,
inefficiently
case
As
ammonia
asfig.
reagent
gas.
general
ionization
behaviour
is comparable
to Sarin
(GB)
ethoxy side
group
of in
Tabun
is7(a)-(c)
split off
andInsubstituted
by
a
Again,
fragmentation
can
be suppressed
by
hydroxyl group analogous to Sarin derivatives.
reducing the drift voltage, as shown in Figure 9(b). A very weak
ofand
water
chemistry
andunder
a driftPTR
voltage
of 600V
intense peaks appear at m/z 117 and m/z
Cyclosarin
(GF)
ionization
conditions.
135 corresponding to the fragment/water clusters discussed before (fig. 7(a)). Protonat(b) 400 V, ammonia chemistry
(a) 600 V, water chemistry
ed Cyclosarin and its water single adduct appear appear with almost the same peak
800
800
700
700
intensity at this drift voltage.
Decreasing
the voltage but keeping water chemistry
leads to almost complete suppres600
600
cps
cps
sion500of fragmentation as in case of Sarin. Fig.
500 7(b) shows the spectrum recorded at
400
400
200V
drift voltage. Remarkably, under those conditions
the water clustered ion species
are preferably formed compared to the just protonated species. This is applicable for
300
300
200
200
100
100
both, the analyte Cyclosarin and its fluoro-methyl-phosphonate fragment.
0
80
100
120
140
m/z
160
180
200
220
17
0
80
100
120
140
m/z
160
180
200
220
Figures 8(a) and (b). PTR-ToF-MS spectra of Soman recorded at different drift voltages and with water and ammonia as reagent
Fig. 8(a)-(b): PTR-ToF-MS spectra of Soman (GD) recorded at different drift voltages
gases.
and with water and ammonia as reagent gases
Obviously due to their structural and chemical similarities Sarin, Cyclosarin and Soman
spectra turn up with same distinct characteristics in terms of fragmentation, clustering
184
Detection of Nerve Agents using PTRMS with Ammonia as the Reagent Gas
(a) 600 V, water chemistry
(c) 300 V, ammonia chemistry
900
900
800
800
700
700
600
500
cps
cps
600
400
500
400
300
300
200
200
100
100
0
0
80
100
120
140
m/z
160
180
200
220
180
200
220
80
100
120
140
m/z
160
180
200
220
(b) 300 V, water chemistry
900
800
700
cps
600
500
400
300
200
100
0
80
100
120
140
m/z
160
Figures 9(a)–(c). PTR-ToF-MS spectra of Tabun recorded at different drift voltages and with water and ammonia as reagent gases.
peakTabun
can be seen
at m/z 199
corresponding
to thefragmentation
double water
species
are formed
at atmospheric
ionisation
(API)
renders
a more
complex
behaviour
than
the Sarin pressure
derivatives.
The
adduct [GA.(H2O)2.H]+. Analogous to GB, GD and GF, s­ ignificant
conditions such as in IMS usually.
Therelated
extent of
suppressed
amounts
of protonated
Tabun in
[GA.H]
appearare
onlyeither
at water
ion species
shown
fig.+ 9(a)
directly
to fragmentation
Tabun (m/z can
163beand
181) or by
choosing low drift voltages and, much more effectively, by
chemistry at m/z 163 [Figures 9(a) and (b)]. The single water
+
can
be2O.H]
traced
back
to fragments
and rearrangement
E.g.
adduct
[GA.H
using ammoniaproducts.
as the reagent
gas. there is a set of
at m/z
181, however,
is most significant,
In any case, and regardless of whether water or ammonia
even at a drift voltage of 600 V.
peaks at m/z 135 and 153. This is due to a rearrangement
product in which the ethoxy
acts as the reagent compound in gas-phase ion chemistry
In Figure 9(c), a Tabun spectrum at ammonia chemistry
at drift
aroundgroup
400 V ionisation
efficiency
reaches
and 300 V
voltage
presented.
peaks
sidedrift
group
ofisTabun
is The
split
off corresponding
and substituted
by voltages
a hydroxyl
analogue
the Sarin
a maximum. Under those conditions, however, nerve agents
to the single and the double ammonia adducts at m/z 180 and
m/z 197
are most significant and predominate in the spec- fragment almost completely at pure water c­ hemistry
derivatives.
which impairs identification with a significantly high level
trum. This, again, is consistent with experiments carried out
fragmentation can be suppressed efficiently
bySuppression
reducing ofthe
drift voltage
as
of ­confidence.
fragmentation
is required
with Again,
the Sarin derivatives.
in respect of unambiguous identification and to dispense
shown in fig. 9(b). A very weak peak can be seen at m/z 199 corresponding to the douwith the need for a time-consuming pre-separation of multi
+
compound
sample
Switching toamounts
ammonia chemble water adduct [GA.(H2O)2.H] . Analogue to GB, GD
andmixtures.
GF significant
of
istry resolves the problem. The drift voltage can be kept
protonated
[GA.H]+ appear
at water
chemistry
at ofm/z
163 (fig.
9(a)-(b)).
The
at 400 V.
In the case
ammonia
chemistry,
fragmentation
It was
found that Tabun
the organophosphonate
andonly
organo­
does not obviously take place and only peaks corresponding
phosphate type nerve agents tend to fragment depending
on the system adjustment, whereas extremely stable ion 19to clusters of unfragmented nerve agents appear, which
Conclusions
J.M. Ringer, Eur. J. Mass Spectrom. 19, 175–185 (2013)185
creates the prerequisites for identification capabilities in
near real time.
On the other hand, detection and identification is then
based on the molecular ion species and not on a distinct
signal pattern. Although agent fragmentation is unfavourable, for some reason this phenomenon can deliver additional structural information and, therefore, confirm the
presence of an agent based on an organophosphorous
basic structure. Fragments such as fluorophosphonic acid do
not allow the unambiguous identification of nerve agents but
they indicate that the unfragmented target compound can be
traced back to a phosphorous organic basic structure and,
therefore, it contributes to an increase i n the level of identification confidence. Seen from this angle, aimed fragmentation at water chemistry is useful in respect of structural
substantiation of data obtained at ammonia chemistry. Of
course, it is also possible to operate a PTR system permanently on water chemistry and switch to ammonia as soon
as distinct fragments such as fluoro-phosphonic appear. In
contrast to IMS, it is easily possible to switch between water
and ammonia chemistry within a few seconds under PTRMS
ionisation conditions at about 2 mbar. Drift voltage may be
changed as well in this context which takes even less time.
Adding ammonia to the sample gas instead of substituting
the water reservoir of the system by an ammonia source
is easy to put into practice and brings another a
­ dvantage:
the initial process of ionisation in the hollow cathode is not
affected under any circumstances. This means that solely
H3O+ are produced initially and, therefore, calculation models
to determine the compound fragmentation should be applicable even if ammonia is added to the drift tube.
Further on, in context of this work, it was found that
PTR-Quad and PTR-ToF-MS spectra recorded under the
same experimental conditions differ from each other
in detail although the PTR hardware should be identical
according the manufacturers statement. Generally, and at
both water and ammonia chemistry, differences concerning
the proportional distribution of protonated species and
their particular reagent gas adduct clusters (single-, doubleand mixed clustered) have been observed. In PTR-ToF-MS
spectra, significantly more reagent gas clusters appear.
Considering the PTR hardware of both systems are identical, this phenomenon is an indication that some reagent
gas clusters might not reach the detector plate in the
PTR-Quad-MS and get lost depending on cluster stability,
the PTRMS interface and/ or the type of mass spectrometer.
If this hypothesis is applicable, the ToF detector is better
suited to nerve agent detection due to less ion losses.
Furthermore, especially at water chemistry, the
­p roportional distribution between fragmented and
­unfragmented agents is different. Less fragmentation has
been observed in PTR-ToF-MS compared to the quadrupole
system. Fragmentation and forming of product ions, however,
takes place in the drift tube. Therefore, this phenomenon
might be an indication of differences in respect of the PTR
hardware. As fragmentation is unfavourable in any case, this
phenomenon also suggests that PTR-ToF-MS is particularly
suited to nerve agent detection.
In overall conclusion, it was found that both PTR-Quad-MS
and PTR-ToF-MS are suitable for detecting nerve agents,
the most toxic agents among CWA, with high sensitivity
and a very high level of confidence in near real-time.
In the end, PTR-ToF-MS seems to be an even more suitable technique for nerve agent detection because o f its
sensitivity and detection rate. Considering that reagent ion
clusters also contribute to total agent concentration, it as
also important that this type of ion species does not drop
away from PTR-ToF-MS.
PTR-ToF-MS is a remarkable and promising technique for
future CWA detector techniques in terms of bridging the
analytical gap between IMS and classical GC-MS in field
applications.
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