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An isomer-specific high-energy collision-induced dissociation MS/MS database for forensic applications: a proof-of-concept on chemical warfare agent markers
Umeå University, Faculty of Science and Technology, Department of Chemistry. (The Swedish Defence Research Agency, FOI CBRN Defence and Security, Umeå, Sweden)
The Swedish Defence Research Agency, FOI CBRN Defence and Security, Umeå, Sweden.
The Swedish Defence Research Agency, FOI CBRN Defence and Security, Umeå, Sweden.
The Swedish Defence Research Agency, FOI CBRN Defence and Security, Umeå, Sweden.
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2011 (English)In: Journal of Mass Spectrometry, ISSN 1076-5174, E-ISSN 1096-9888, Vol. 46, no 9, 917-924 p.Article in journal (Refereed) Published
Abstract [en]

Spectra database search has become the most popular technique for the identification of unknown chemicals, minimizing the need for authentic reference chemicals. In the present study, an isomer-specific high-energy collision-induced dissociation (CID) MS/MS spectra database of 12 isomeric O-hexyl methylphosphonic acids (degradation markers of nerve agents) was created. Phosphonate anions were produced by the electrospray ionization of phosphonic acids or negative-ion chemical ionization of their fluorinated derivatives and were analysed in a hybrid magnetic-sector–time-of-flight tandem massspectrometer. A centre-of-mass energy (Ecom) of 65eV led to an optimal sequential carbon–carbon bond breakage, which was interpreted in terms of charge remote fragmentation. The proposed mechanism is discussed in comparison with the routinely used low-energy CID MS/MS. Even-mass (odd-electron) charge remote fragmentation ion series were diagnostic of the O-alkyl chain structure and can be used to interpret unknown spectra. Together with the odd-mass ion series, they formed highly reproducible, isomer-specific spectra that gave significantly higher database matches and probability factors (by 1.5 times) than did the EI MS spectra of the trimethylsilyl derivatives of the same isomers. In addition, ionization by negative-ion chemical ionization and electrospray ionization resulted in similar spectra, which further highlights the general potential of the high-energy CID MS/MS technique.  

Place, publisher, year, edition, pages
Wiley , 2011. Vol. 46, no 9, 917-924 p.
Keyword [en]
HE CID, MS/MS database, nerve agents, alkylphosphonic acids, charge remote fragmentation
National Category
Chemical Sciences
URN: urn:nbn:se:umu:diva-46524DOI: 10.1002/jms.1970OAI: diva2:438628
Available from: 2011-09-05 Created: 2011-09-05 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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