Identification of adducts formed between phosphatidylcholine and mustard agents
Matti A Kjellberg1, Noora-Kaisa Rantanen2, Shishir Jaikishan3
1Finnish Institute for Verification of the Chemical Weapons Convention (VERIFIN), Department of Chemistry, University of Helsinki, A.I. Virtasen Aukio 1, POB 55, 00014, Helsinki, Finland. matti.kjellberg@helsinki.fi.
Abstract:
Sulphur and nitrogen mustards are two groups of highly toxic blistering agents. Upon human exposure, these agents produce characteristic biomarkers, including alkylated proteins and DNA. In contrast, lipids, which comprise a varied class of biomolecules, have received little attention as potential alkylation targets of mustard agents. In this work, we demonstrate that sulphur and nitrogen mustards bind covalently to 1-palmitoyl-2-oleoyl-glycero-sn-3-phosphocholine in model membrane systems. We use ultra-high-performance liquid chromatography-high-resolution tandem mass spectrometry to characterise the structures of these novel analytes. Additionally, alkylated phosphatidylcholines were detectable in human plasma spiked with trace concentrations of sulphur mustard. Plasma samples were prepared by liquid-liquid extraction and analysed by targeted multi-reaction monitoring ultra-high-performance liquid chromatography-tandem mass spectrometry. Our data suggest that these novel alkylated lipids may function as biomarkers of mustard agent exposure.
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