PMID- 34215915
OWN - NLM
STAT- MEDLINE
DCOM- 20211019
LR  - 20211021
IS  - 1618-2650 (Electronic)
IS  - 1618-2642 (Print)
IS  - 1618-2642 (Linking)
VI  - 413
IP  - 19
DP  - 2021 Aug
TI  - Alkylated albumin-derived dipeptide C(-HETE)P derivatized by propionic anhydride 
      as a biomarker for the verification of poisoning with sulfur mustard.
PG  - 4907-4916
LID - 10.1007/s00216-021-03454-w [doi]
AB  - Sulfur mustard (SM) is a banned chemical warfare agent recently used in the 
      Syrian Arab Republic conflict causing erythema and blisters characterized by 
      complicated and delayed wound healing. For medical and legal reasons, the proof 
      of exposure to SM is of high toxicological and forensic relevance. SM reacts with 
      endogenous human serum albumin (HSA adducts) alkylating the thiol group of the 
      cysteine residue C(34), thus causing the addition of the hydroxyethylthioethyl 
      (HETE) moiety. Following proteolysis with pronase, the biomarker dipeptide 
      C(-HETE)P is produced. To expand the possibilities for verification of exposure, 
      we herein introduce a novel biomarker produced from that alkylated dipeptide by 
      derivatization with propionic anhydride inducing the selective propionylation of 
      the N-terminus yielding PA-C(-HETE)P. Quantitative derivatization is carried out 
      at room temperature in aqueous buffer within 10 s. The biomarker was found to be 
      stable in the autosampler at 15  degrees C for at least 24 h, thus documenting its 
      suitability even for larger sets of samples. Selective and sensitive detection is 
      done by micro liquid chromatography-electrospray ionization tandem-mass 
      spectrometry (muLC-ESI MS/MS) operating in the selected reaction monitoring (SRM) 
      mode detecting product ions of the single protonated PA-C(-HETE)P (m/z 379.1) at 
      m/z 116.1, m/z 137.0, and m/z 105.0. The lower limit of detection corresponds to 
      32 nM SM in plasma in vitro and the limit of identification to 160 nM. The 
      applicability to real exposure scenarios was proven by analyzing samples from the 
      Middle East confirming poisoning with SM.
CI  - (c) 2021. The Author(s).
FAU - Richter, Annika
AU  - Richter A
AD  - Department of Chemistry, Humboldt-Universitat zu Berlin, Brook-Taylor-Strasse 2, 
      12489, Berlin, Germany.
FAU - Siegert, Markus
AU  - Siegert M
AD  - Department of Chemistry, Humboldt-Universitat zu Berlin, Brook-Taylor-Strasse 2, 
      12489, Berlin, Germany.
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937, 
      Munich, Germany.
FAU - Thiermann, Horst
AU  - Thiermann H
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937, 
      Munich, Germany.
FAU - John, Harald
AU  - John H
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937, 
      Munich, Germany. HaraldJohn@bundeswehr.org.
LA  - eng
GR  - Research Training Group GRK 2338/Deutsche Forschungsgemeinschaft/
PT  - Journal Article
DEP - 20210702
PL  - Germany
TA  - Anal Bioanal Chem
JT  - Analytical and bioanalytical chemistry
JID - 101134327
RN  - 0 (Albumins)
RN  - 0 (Anhydrides)
RN  - 0 (Biomarkers)
RN  - 0 (Chemical Warfare Agents)
RN  - 0 (Dipeptides)
RN  - 0 (Propionates)
RN  - E3A2VV18E6 (propionic anhydride)
RN  - T8KEC9FH9P (Mustard Gas)
SB  - IM
MH  - Albumins/*chemistry
MH  - Alkylation
MH  - Anhydrides/*chemistry
MH  - Biomarkers
MH  - Chemical Warfare Agents/*poisoning
MH  - Dipeptides/*chemistry
MH  - Humans
MH  - Mustard Gas/*poisoning
MH  - Propionates/*chemistry
PMC - PMC8318952
OTO - NOTNLM
OT  - Biomarker
OT  - Chemical warfare agent
OT  - HETE moiety
OT  - Propionic anhydride
OT  - Protein adduct
OT  - Verification
COIS- The authors declare no competing interests.
EDAT- 2021/07/04 06:00
MHDA- 2021/10/21 06:00
PMCR- 2021/07/02
CRDT- 2021/07/03 06:12
PHST- 2021/04/29 00:00 [received]
PHST- 2021/06/04 00:00 [accepted]
PHST- 2021/05/25 00:00 [revised]
PHST- 2021/07/04 06:00 [pubmed]
PHST- 2021/10/21 06:00 [medline]
PHST- 2021/07/03 06:12 [entrez]
PHST- 2021/07/02 00:00 [pmc-release]
AID - 10.1007/s00216-021-03454-w [pii]
AID - 3454 [pii]
AID - 10.1007/s00216-021-03454-w [doi]
PST - ppublish
SO  - Anal Bioanal Chem. 2021 Aug;413(19):4907-4916. doi: 10.1007/s00216-021-03454-w. 
      Epub 2021 Jul 2.