Title
Mass spectrometric analysis of adducts of sulfur mustard analogues to human plasma proteins: approach towards chemical provenancing in biomedical samples
Author
Hemme, M.
Fidder, A.
van der Riet-van Oeveren, D.
van der Schans, M.J.
Noort, D.
Publication year
2021
Abstract
The primary aim of this study was to identify biomarkers of exposure to some so-called Schedule 1 sulfur mustard (HD) analogues, in order to facilitate and expedite their retrospective analysis in case of alleged use of such compounds. Since these HD analogues can be regarded as model compounds for possible impurities of HD formed during synthesis processes, the secondary aim was to explore to which extent these biomarkers can be used for chemical provenancing of HD in case biomedical samples are available. While the use of chemical attribution signatures (CAS) for neat chemicals or for environmental samples has been addressed quite frequently, the use of CAS for investigating impurities in biomedical samples has been addressed only scarcely. Human plasma was exposed to each of the five HD analogues. After pronase or proteinase K digestion of precipitated protein and sample work-up, the histidine (His) and tripeptide (CPF) adducts to proteins were analyzed, respectively. Adducts of the analogues could still be unambiguously identified next to the main HD adducts in processed plasma samples after exposure to HD mixed with each of the analogues, at a 1% level relative to HD. In conclusion, we have identified plasma protein adducts of a number of HD analogues, which can be used as biomarkers to assess an exposure to these Schedule 1 chemicals. We have shown that adducts of these analogues can still be analyzed after work-up of plasma samples which had been exposed to these analogues in a mixture with HD, supporting the hypothesis that biomedical sample analysis might be useful for chemical provenancing.
Subject
Analogues
Chemical attribution signatures
Chemical warfare agent
LC-MS/MS
Protein adductS
Sulfur mustard
Amino acids
Biomarkers
Indicators (chemical)
Mass spectrometry
Plasma (human)
Proteins
Sulfur
Environmental sample
Human plasma proteins
Mass spectrometric analysis
Model compound
Precipitated proteins
Retrospective analysis
Sample analysis
Synthesis process
Chemical analysis
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http://resolver.tudelft.nl/uuid:7af04493-1843-4744-aea6-7930f1e020ff
DOI
https://doi.org/10.1007/s00216-021-03354-z
TNO identifier
955938
ISSN
1618-2642
Source
Analytical and Bioanalytical Chemistry, 413 (413), 4023-4036
Bibliographical note
The Netherlands Ministry of Defence is gratefully acknowledged for funding this work ; This research was supported by The Netherlands Ministry of Defence.
Document type
article