期刊
DRUG TESTING AND ANALYSIS
卷 13, 期 9, 页码 1593-1602出版社
WILEY
DOI: 10.1002/dta.3114
关键词
biomarker; chemical warfare agent; HETE-moiety; protein-adduct; verification
资金
- German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) [GRK 2338]
Sulfur mustard is a banned chemical warfare agent that can be analyzed post-exposure by detecting human serum albumin-derived peptides. A novel procedure for selective precolumn nicotinylation of its N-terminus has been presented in this study.
Sulfur mustard (SM, bis[2-chloroethyl]-sulfide) is a banned chemical warfare agent that was frequently used in recent years and led to numerous poisoned victims who developed painful erythema and blisters. Post-exposure analysis of SM incorporation can be performed by the detection of human serum albumin (HSA)-derived peptides. HSA alkylated by SM contains a hydroxyethylthioethyl (HETE)-moiety bound to the cysteine residue C-34 yielding the dipeptide biomarker C(-HETE)P after pronase-catalyzed proteolysis. We herein present a novel procedure for the selective precolumn nicotinylation of its N-terminus using 1-nicotinoyloxy-succinimide. The reaction was carried out for 2 h at ambient temperature with a yield of 81%. The derivative NA-C(-HETE)P was analyzed by micro liquid chromatography-electrospray ionization tandem-mass spectrometry working in the selected reaction monitoring mode (mu LC-ESI MS/MS SRM). The derivative was shown to be stable in the autosampler at 15 degrees C for at least 24 h. The single protonated precursor ion (m/z 428.1) was subjected to collision-induced dissociation yielding product ions at m/z 116.1, m/z 137.0, and m/z 105.0 used for selective monitoring without any plasma-derived interferences. NA-C(-HETE)P showed a mass spectrometric response superior to the non-derivatized dipeptide thus yielding larger peak areas (factor 1.3 +/- 0.2). The lower limit of identification corresponded to 80 nM SM spiked to plasma in vitro. The presented procedure was applied to real case plasma samples from 2015 collected in the Middle East confirming SM poisoning.
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