PMID- 34145783
OWN - NLM
STAT- MEDLINE
DCOM- 20220121
LR  - 20220121
IS  - 1942-7611 (Electronic)
IS  - 1942-7603 (Linking)
VI  - 13
IP  - 9
DP  - 2021 Sep
TI  - Evidence of sulfur mustard poisoning by detection of the albumin-derived 
      dipeptide biomarker C(-HETE)P after nicotinylation.
PG  - 1593-1602
LID - 10.1002/dta.3114 [doi]
AB  - 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 (muLC-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.
CI  - (c) 2021 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.
FAU - John, Harald
AU  - John H
AUID- ORCID: 0000-0002-7126-6709
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany.
FAU - Richter, Annika
AU  - Richter A
AD  - Department of Chemistry, Humboldt-Universitat zu Berlin, Berlin, Germany.
FAU - Thiermann, Horst
AU  - Thiermann H
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany.
LA  - eng
GR  - GRK 2338/German Research Foundation/
PT  - Journal Article
PT  - Validation Study
DEP - 20210623
PL  - England
TA  - Drug Test Anal
JT  - Drug testing and analysis
JID - 101483449
RN  - 0 (Biomarkers)
RN  - 0 (Chemical Warfare Agents)
RN  - 0 (Dipeptides)
RN  - 2679MF687A (Niacin)
RN  - T8KEC9FH9P (Mustard Gas)
RN  - ZIF514RVZR (Serum Albumin, Human)
SB  - IM
MH  - Biomarkers/analysis
MH  - Chemical Warfare Agents/*analysis/chemistry/poisoning
MH  - Chromatography, Liquid/*methods
MH  - Dipeptides/chemistry
MH  - Humans
MH  - Mustard Gas/*analysis/chemistry/poisoning
MH  - Niacin/chemistry
MH  - Serum Albumin, Human/chemistry
MH  - Spectrometry, Mass, Electrospray Ionization
MH  - Tandem Mass Spectrometry/*methods
OTO - NOTNLM
OT  - HETE-moiety
OT  - biomarker
OT  - chemical warfare agent
OT  - protein-adduct
OT  - verification
EDAT- 2021/06/20 06:00
MHDA- 2022/01/22 06:00
CRDT- 2021/06/19 06:44
PHST- 2021/06/13 00:00 [revised]
PHST- 2021/04/29 00:00 [received]
PHST- 2021/06/13 00:00 [accepted]
PHST- 2021/06/20 06:00 [pubmed]
PHST- 2022/01/22 06:00 [medline]
PHST- 2021/06/19 06:44 [entrez]
AID - 10.1002/dta.3114 [doi]
PST - ppublish
SO  - Drug Test Anal. 2021 Sep;13(9):1593-1602. doi: 10.1002/dta.3114. Epub 2021 Jun 
      23.