PMID- 25712440
OWN - NLM
STAT- MEDLINE
DCOM- 20160121
LR  - 20150421
IS  - 1945-2403 (Electronic)
IS  - 0146-4760 (Linking)
VI  - 39
IP  - 4
DP  - 2015 May
TI  - Evidence of Sulfur Mustard Exposure in Human Plasma by LC-ESI-MS-MS Detection of 
      the Albumin-Derived Alkylated HETE-CP Dipeptide and Chromatographic Investigation 
      of Its Cis/Trans Isomerism.
PG  - 270-9
LID - 10.1093/jat/bkv010 [doi]
AB  - Sulfur mustard (SM) is a chemical warfare agent that causes painful blisters and 
      chemically modifies endogenous biomacromolecules by alkylation to 
      hydroxyethylthioethyl (HETE) adducts representing valuable long-term markers for 
      post-exposure analysis. The albumin adduct formed in human plasma in vitro (HETE 
      bound to the side chain of cysteine 34) was isolated and cleaved by current lots 
      of pronase primarily generating the internal modified dipeptide 
      (HETE-cysteine-proline, HETE-CP) instead of the formerly reported HETE-CPF 
      tripeptide. The analyte was detected by liquid chromatography-electrospray 
      ionization tandem-mass spectrometry (LC-ESI-MS-MS). In principle, HETE-CP 
      undergoes a dynamic on-column equilibrium of cis-trans isomerism thus requiring 
      separation at 50 degrees C to obtain one narrow peak. Accordingly, we developed both a 
      novel longer lasting but more sensitive microbore (1 mm i.d., flow 30 microL/min, 
      cycle time 60 min, LOD 50 nM) and a faster, less sensitive narrowbore (2.1 mm 
      i.d., 200 microL/min, cycle time 16 min, LOD 100 nM, both on Atlantis T3 material at 
      50 degrees C) LC-ESI-MS-MS method suitable for verification analysis. The corresponding 
      tri- and tetrapeptide, Q(HETE)-CPF were monitored simultaneously. HETE-CP peak 
      areas were directly proportional to SM concentrations added to plasma in vitro 
      (0.05-100 microM). Albumin adducts formed by deuterated SM (d8-SM) served as internal 
      standard.
CI  - (c) The Author 2015. Published by Oxford University Press. All rights reserved. For 
      Permissions, please email: journals.permissions@oup.com.
FAU - Gandor, Felix
AU  - Gandor F
AD  - Department of Chemistry, Humboldt-Universitat zu Berlin, Berlin, Germany.
FAU - Gawlik, Michael
AU  - Gawlik M
AD  - Hamm-Lippstadt University of Applied Sciences, Biomedical Engineering, Hamm, 
      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
PT  - Journal Article
DEP - 20150221
PL  - England
TA  - J Anal Toxicol
JT  - Journal of analytical toxicology
JID - 7705085
RN  - 0 (Biomarkers)
RN  - 0 (Chemical Warfare Agents)
RN  - 0 (Dipeptides)
RN  - 0 (Serum Albumin)
RN  - 70873-84-6 (cysteinylproline)
RN  - EC 3.4.24.- (Pronase)
RN  - T8KEC9FH9P (Mustard Gas)
SB  - IM
MH  - Alkylation
MH  - Biomarkers/blood
MH  - Chemical Warfare Agents/chemistry/*poisoning
MH  - Chromatography, Liquid/*methods
MH  - Dipeptides/*blood/chemistry
MH  - Humans
MH  - Hydroxylation
MH  - Limit of Detection
MH  - Mustard Gas/chemistry/*poisoning
MH  - Poisoning/blood
MH  - Pronase/chemistry
MH  - Protein Binding
MH  - Proteolysis
MH  - Serum Albumin/*chemistry
MH  - Spectrometry, Mass, Electrospray Ionization/*methods
MH  - Tandem Mass Spectrometry/*methods
EDAT- 2015/02/26 06:00
MHDA- 2016/01/23 06:00
CRDT- 2015/02/26 06:00
PHST- 2015/02/26 06:00 [entrez]
PHST- 2015/02/26 06:00 [pubmed]
PHST- 2016/01/23 06:00 [medline]
AID - bkv010 [pii]
AID - 10.1093/jat/bkv010 [doi]
PST - ppublish
SO  - J Anal Toxicol. 2015 May;39(4):270-9. doi: 10.1093/jat/bkv010. Epub 2015 Feb 21.