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Determination of S-2-(N,N-diisopropylaminoethyl)- and S-2-(N,N-diethylaminoethyl) methylphosphonothiolate, nerve agent markers, in water samples using strong anion-exchange disk extraction, in vial trimethylsilylation, and gas chromatography-mass spectrometry analysis
Umeå University, Faculty of Science and Technology, Department of Chemistry. (The Swedish Defence Research Agency, FOI CBRN Defence and Security, SE-901 82 Umeå, Sweden)
The Swedish Defence Research Agency, FOI CBRN Defence and Security, SE-901 82 Umeå, Sweden.
The Swedish Defence Research Agency, FOI CBRN Defence and Security, SE-901 82 Umeå, Sweden.
The Swedish Defence Research Agency, FOI CBRN Defence and Security, SE-901 82 Umeå, Sweden.
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2012 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1229, 86-94 p.Article in journal (Refereed) Published
Abstract [en]

Since the establishment of the Chemical Weapons Convention in 1997, the development of analytical methods for unambiguous identification of large numbers of chemicals related to chemical warfare agents has attracted increased interest. The analytically challenging, zwitterionic S-2-(N,N-diisopropylaminoethyl) methylphosphonothiolate (EA-2192), a highly toxic degradation marker of the nerve agent VX, has been reported to resist trimethylsilylation or to result in an unacceptably high limit of detection in GC-MS analysis. In the present study, the problem is demonstrated to be associated with the presence of salt, which hinders trimethysilylation. EA-2192 was extracted from aqueous samples by use of a strong anion-exchange disk, derivatized as a trimethylsilyl derivative via in vial solid-phase trimethylsilylation and identified by GC-MS. The limits of detection were 10ng/mL and 100ng/mL (in a water sample) for SIM and SCAN mode respectively. The analytical method was found to be repeatable with relative standard deviation <10%. The performance of the method was evaluated using a proficiency test sample and environmental samples (spiked river water and Baltic Bay water) and compared with the commonly used evaporation-silylation method. The disk method displayed good tolerance to the presence of salt and the spiked EA-2192 was conclusively identified in all matrices. In addition, the applicability of the method was further demonstrated for other selected hydrolysis products of VX and Russian VX, namely S-2-(N,N-diethylaminoethyl) methylphosphonothiolate, ethyl methylphosphonic acid, methylphosphonic acid, and isobutyl methylphosphonic acid. For the synthesis of reference compounds, EA-2192 and its analog from degradation of the Russian VX isomer, the present methods were improved by using a polymer-bound base, resulting in >90% purity based on (1)H NMR. Based on the current results and earlier work on alkylphosphonic acids using the same method, we conclude that the method is a viable choice for the simultaneous determination of a wide range of degradation products of nerve agents - zwitterionic, monoacid, diacid, and monothioacid chemicals - with excellent performance.

Place, publisher, year, edition, pages
Amsterdam: Elsevier, 2012. Vol. 1229, 86-94 p.
Keyword [en]
Chemical warfare agents, EA-2192, Silylation, Alkylphosphonic acid, Solid-phase derivatization, Anion-exchange disk
National Category
Chemical Sciences
URN: urn:nbn:se:umu:diva-52430DOI: 10.1016/j.chroma.2012.01.068PubMedID: 22326187OAI: diva2:504602
Available from: 2012-02-21 Created: 2012-02-21 Last updated: 2012-05-04Bibliographically approved
In thesis
1. Simplified Routines for Sample Preparation and Analysis of Chemical Warfare Agent Degradation Products
Open this publication in new window or tab >>Simplified Routines for Sample Preparation and Analysis of Chemical Warfare Agent Degradation Products
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The thesis describes the development of new and improved methods for analyzing degradation markers from organophosphorus Chemical Warfare Agents (CWAs).

Paper I and II describes an innovative and significantly improved method for the enrichment, derivatization (trimethysilylation) and GC-MS analysis of a broad range of organophosphorus CWAs degradation markers, namely the alkylphosphonic acids and a zwitterionic compound. That was achieved using solid phase disc extraction in combination with solid phase derivatization. The new method overcomes most limitations observed with existing techniques: it offers almost 100 % recoveries, requires no elution or evaporation steps, facilitates miniaturization of the solid sorbent and reagent, is compatible with in-vial derivatization, and minimizes the chromatographic background due to the use of a highly selective anion exchange sorbent disc.

Paper III describes the development of new fluorinated diazomethane derivatization reagents and their evaluation for rapid and high sensitivity screening and identification of nerve agent degradation markers. The reagents are water-tolerant to some extent, which simplifies the derivatization step. The best reagent identified was 3,5-bis(trifluoromethyl)benzyl diazomethane, which outperformed the other reagent isomers tested and also the established commercial alternative, pentafluorobenzylbromide, allowing for the rapid (5 min) and direct derivatization of a 25 μL aqueous sample in acetonitrile. The spectra of the formed derivatives (high-energy collision induced fragmentation MS/MS) were used to construct a database (Paper IV) that proved to be superior in terms of match factor and probability compared to EI data gathered for trimethylsilyl derivatives. The study also focused on efforts towards achieving detailed structure information on the alkyl chains of the compounds in question using diagnostic ion interpretation.

The final paper (paper V) describes the first rapid direct derivatization method for analyzing nerve agent metabolites in urine at trace levels. The method is based on the derivative from the paper III and the unambiguous identification was proven using a combination of low resolution and high resolution negative ion chemical ionization selected ion monitoring techniques.

Novel results presented in these papers include: the first in-situ derivatization of alkylphosphonic acids on an SPE disc; the first direct derivatization of nerve agent markers in water and biomedical samples; the first high sensitivity GC-MS screening for these markers; and the first highly reproducible high-energy isomer specific CID MS/MS library. Overall, the results presented in this thesis represent significant contributions to the analysis of nerve agent degradation products.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2012. 58 p.
Nerve agents, Alkyl alkylphosphonic acids, Solid phase derivatization, Fluorinated diazomethane reagent, High-energy collision induced dissociation, CID MS/MS library
National Category
Chemical Sciences
Research subject
Analytical Chemistry
urn:nbn:se:umu:diva-54639 (URN)978-91-7459-440-9 (ISBN)
Public defence
2012-05-25, KB3B1, KBC-huset, Umeå University, Umeå, 09:00 (English)
Available from: 2012-05-04 Created: 2012-05-03 Last updated: 2012-05-04Bibliographically approved

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