Development of a Liquid Chromatography-Multiple Reaction Monitoring Procedure for Concurrent Verification of Exposure to Different Forms of Mustard Agents

A novel liquid chromatography-multiple reaction monitoring (LC-MRM) procedure has been developed for retrospective diagnosis of exposure to different forms of mustard agents. This concise method is able to validate prior exposure to nitrogen mustards (HN-1, HN-2, and HN-3) or sulfur mustard (HD) in...

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Bibliographic Details
Published in:Journal of analytical toxicology 2008-01, Vol.32 (1), p.51-56
Main Authors: Yeo, Thong-Hiang, Ho, Mer-Lin, Loke, Weng-Keong
Format: Article
Language:English
Subjects:
Alkylation
Biomarkers - blood
Chromatography, Affinity
Chromatography, Liquid - methods
Computational Biology - methods
Environmental Exposure - analysis
Environmental Monitoring - methods
Humans
Mechlorethamine - analysis
Mechlorethamine - metabolism
Mustard Compounds - analysis
Mustard Compounds - metabolism
Mustard Gas - analysis
Mustard Gas - metabolism
Nitrogen Mustard Compounds - analysis
Nitrogen Mustard Compounds - metabolism
Reproducibility of Results
Serum Albumin - chemistry
Serum Albumin - isolation & purification
Serum Albumin - metabolism
Software
Solid Phase Extraction
Tandem Mass Spectrometry - methods
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Summary:A novel liquid chromatography-multiple reaction monitoring (LC-MRM) procedure has been developed for retrospective diagnosis of exposure to different forms of mustard agents. This concise method is able to validate prior exposure to nitrogen mustards (HN-1, HN-2, and HN-3) or sulfur mustard (HD) in a single run, which significantly reduces analysis time compared to separate runs to screen for different mustards' biomarkers based on tandem mass spectrometry. Belonging to one of the more toxic classes of chemical warfare agents, these potent vesicants bind covalently to the cysteine-34 residue of human serum albumin. This results in the formation of stable adducts whose identities were confirmed by a de novo sequencing bioinformatics software package. Our developed technique tracks these albumin-derived adduct biomarkers in blood samples which persist in vitro following exposure, enabling a detection limit of 200nM of HN-1, 100nM of HN-2, 200nM of HN-3, or 50nM of HD in human blood. The CWA-adducts formed in blood samples can be conveniently and sensitively analyzed by this MRM technique to allow rapid and reliable screening.
ISSN:0146-4760
1945-2403
DOI:10.1093/jat/32.1.51