Assuring Quality in the Analytical Lab:
Certified Reference Materials for Gas
Chromatography
Frank Michel1, Christine Hellriegel2, Alexander Rueck2
1 Sigma Aldrich Chemie GmbH, a subsidiary of Merck group, Eschenstrasse 5, 82024 Taufkirchen, Germany,
[email protected]; 2 Sigma-Aldrich Chemie GmbH, Industriestrasse 25, 9471 Buchs SG, Switzerland
Introduction
Content Assignment by qNMR
The regular use of Certified Reference Materials (CRMs) is an
important and crucial part within the scope of quality assurance in
analytical laboratories beside of other activities. Laboratories
accredited to ISO 17025 have got to use CRMs on a regular base, if
they are available.
Experimental
Measurements were conducted on a Bruker Avance III 600 MHz NMR
spectrometer. The R&D lab of Sigma-Aldrich Switzerland is fully
accredited under both ISO/IEC 17025 and ISO Guide 34, and highperformance 1H-qNMR (HP-qNMR®) was used for the quantification of
analytes from different substance classes usually used in GC such as
polyaromatic hydrocarbons (PAH), pesticides, natural substances, and
fatty acid esters (Fig. 1). A typical expanded measurement
uncertainty (k=2) is in the range of 0.1 % and makes these
substances ideally suited as Certified Reference Materials (CRM).
Reference for Traceability
(i.e. SRM from NIST)
Dimethylsulfone
Acenaphthene
4 protons
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
6 protons
3.5
3.0
2.5
2.0
1.5
1.0
Fig. 2: HP-qNMR spectrum of Acenaphthene (sample) and Dimethylsulfone as a NIST-traceable
internal qNMR standard
I CRM N Ref M CRM WRef b Ref
PCRM 




 PRef
I Ref N CRM M Ref WCRM b CRM
bCRM
bRef
ICRM
IRef
MCRM
MRef
Buoyancy correction factor for the CRM / [-]
Buoyancy correction factor for the reference / [-]
Value of the integral of the chosen CRM signal / [-]
Value of the integral of the chosen reference signal / [-]
Molecular mass of the CRM / [g mol-1]
Molecular mass of the reference / [g mol-1]
NCRM
NRef
PCRM
PRef
W CRM
W Ref
Number of protons generating the CRM signal / [-]
Number of protons generating the reference signal / [-]
Content of the CRM as mass fraction / [%]
Content of the reference as mass fraction / [%]
Initial weight of the CRM / [g]
Initial weight of the reference / [g]
Fig. 3: Formula for calculation of the content of the CRM
Molecular mass
Reference
(MRef)
Mass
Reference
(mRef)
Content
Reference
(PRef)
Intensity
Reference
(IRef)
Weighing value
Atomic mass
Buoyancy correction
Certified
Content
(PCRM)
Compatibility check
Weighing value
(chemical interaction, impurities)
Atomic mass
Buoyancy correction
Candidate for Certification
High Precision Weighing
Sample Homogeneity
Mass
CRM
(mCRM)
Molecular mass
CRM
(MCRM)
Intensity
CRM
(ICRM)
Rep
Fig. 4: Cause-effect diagram of uncertainty contributions to qNMR measurement
(10 subsamples with qNMR)
Absolute Purity Determination
(10 subsamples with qNMR)
Stability Stress Test
(high T for days)
Certified Value & Uncertainty
Review and Certification
Long Term Stability
(storing T for months)
Additional Characterisation
Certified Reference Material
(HPLC, LC-MS, GC, CHN, mp,
titration, trace impurities, others)
according to
ISO/ IEC 17025 and ISO Guide 34
0.5 ppm
100.0000
This poster presents how qNMR overcomes these challenges in
content assignment and its application for the generation of new
Certified Reference Materials for Gas Chromatography.
Analyte
112.2648
Over the last years quantitative NMR (qNMR) has evolved not only in
pharmaceutical industry but also in many other areas [1]. The
method has several advantages for content determination or the
quantitative evaluation of impurities. The most outstanding attribute
of 1H-qNMR is that it is a relative primary method. The signal
intensity is directly proportional to the number of protons contributing
to the resonance independent of the chemical structure [2]. Due to
this the signal intensities of the sample of interest and a reference
substance can be directly compared. Therefore a direct traceability to
internationally accepted reference standards (e.g. from NIST) can be
achieved [3], which is usually not possible with chromatographic
techniques such as GC.
Internal Standard
Content known
NIST traceable
Summary
With the approach of qNMR the content of organic compounds can be
assigned independent of their chemical identity. The traceability is
ensured by qNMR being a relative primary method. Furthermore
qNMR provides low uncertainties (expanded measurement uncertainty
in the range of 0.1 %).
Based on this approach Certified Reference Materials of the organic
compounds classes polycyclic aromatic hydrocarbons, polychlorinated
biphenyls, pesticides, semi-volatile compounds, plasticizers and fatty
acid methyl esters for GC were created.
Fig. 1: Creation of a Certified Reference Material
References
[1] Weber M, Hellriegel C, “Zertifizierte Standards für die qNMR”, GIT Labor-Fachzeitschrift 2010, 07, 527
[2] Malz F, Jancke H, “Validation of quantitative NMR”, J Pharm Biomed Anal. (2005), 38(5):813-23
[3] Eurachem/CITAC Guide, 1-37, 1st Ed. (2003) “Traceability in chemical measurement”
www.sigma-aldrich.com/organiccrm