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Mass spectrometric analysis of adducts of sulfur mustard analogues to human plasma proteins: approach towards chemical provenancing in biomedical samples

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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.

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Abbreviations

CAS:

Chemical attribution signature(s)

CAS number:

Chemical Abstracts Services number

CPF:

Cysteine-proline-phenylalanine tripeptide

CTA:

Chemical threat agent

CWA:

Chemical warfare agent

CWC:

Chemical Weapons Convention

EIC:

Extracted ion chromatogram

et al.:

et alii/ et alia (and others)

FFM:

Fact-Finding Mission

GB:

Sarin; (RS)-propane-2-yl methylphosphonofluoridate

GC:

Gas chromatography

HETE:

2-((2-Hydroxyethyl)thio)-ethyl

HETE-His:

(2-((2-Hydroxyethyl)thio)-ethyl) histidine

HD:

Sulfur mustard; bis(2-chloroethyl) sulfide

HR:

High resolution

HSA:

Human serum albumin

LC:

Liquid chromatography

LOD:

Limit of detection

MeCN:

Acetonitrile

MRM:

Multiple reaction monitoring

MS:

Mass spectrometry

MS/MS:

Tandem mass spectrometry

NMR:

Nuclear magnetic resonance

OCAD:

OPCW Central Analytical Database

OPCW:

Organisation for the Prohibition of Chemical Weapons

Q:

Sesquimustard; 1,2-bis(2-chloroethylthio) ethane

QTOF:

Quadrupole time-of-flight

RT:

Retention time

SOP:

Standard operating procedure

SPE:

Solid-phase extraction

TDG:

Thiodiglycol

TIC:

Total ion chromatogram

TIM:

Toxic industrial material

TNO:

The Netherlands Organisation for Applied Scientific Research

TS:

Technical Secretariat

U(H)PLC:

Ultra (high)-performance liquid chromatography

WMD:

Weapons of mass destruction

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Acknowledgements

The Netherlands Ministry of Defence is gratefully acknowledged for funding this work.

Funding

This research was supported by The Netherlands Ministry of Defence.

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Author notes

  1. Maria Hemme

    Present address: Bundeswehr Research Institute for Protective Technologies and NBC Protection (WIS), Humboldtstraße, 29633, Munster, Germany

Authors and Affiliations

  1. Chemistry Department, University of Hamburg, Martin-Luther-King-Platz 6, 20146, Hamburg, Germany

    Maria Hemme

  2. Department of CBRN Protection, TNO Defence, Safety & Security, P.O. Box 45, 2280 AA, Rijswijk, The Netherlands

    Maria Hemme, Alex Fidder, Debora van der Riet-van Oeveren, Marcel J. van der Schans & Daan Noort

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  1. Maria Hemme
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Correspondence to Daan Noort.

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Hemme, M., Fidder, A., van der Riet-van Oeveren, D. et al. Mass spectrometric analysis of adducts of sulfur mustard analogues to human plasma proteins: approach towards chemical provenancing in biomedical samples. Anal Bioanal Chem 413, 4023–4036 (2021). https://doi.org/10.1007/s00216-021-03354-z

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