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Evidence of sulfur mustard poisoning by detection of the albumin‐derived dipeptide biomarker C(‐HETE)P after nicotinylation
- Source :
- Drug Testing and Analysis. 13:1593-1602
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- 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 C34 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 (μLC-ESI MS/MS SRM). The derivative was shown to be stable in the autosampler at 15°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.
- Subjects :
- Spectrometry, Mass, Electrospray Ionization
Pharmaceutical Science
Serum Albumin, Human
Protonation
Mass spectrometry
Niacin
01 natural sciences
Analytical Chemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Tandem Mass Spectrometry
Mustard Gas
medicine
Humans
Environmental Chemistry
Chemical Warfare Agents
030216 legal & forensic medicine
Spectroscopy
Chromatography
Dipeptide
Chemistry
010401 analytical chemistry
Selected reaction monitoring
Sulfur mustard
Dipeptides
Human serum albumin
0104 chemical sciences
Biomarkers
Derivative (chemistry)
Chromatography, Liquid
medicine.drug
Cysteine
Subjects
Details
- ISSN :
- 19427611 and 19427603
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Drug Testing and Analysis
- Accession number :
- edsair.doi.dedup.....f39783ac3e6a437ffdecb657b1e0be32