Gas chromatographic–tandem mass spectrometric analysis of β-lyase metabolites of sulfur mustard adducts with glutathione in urine and its use in a rabbit cutaneous exposure model

•A sensitive GC–MS/MS method was established and validated for quantitation of β-lyase metabolites of sulfur mustard.•SPE clean-up procedure was optimized in particular to yield high recoveries and very clean extracts.•The method was applied in a rabbit cutaneous exposure model for the first time.•T...

Full description

Saved in:
Bibliographic Details
Published in:Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2014-01, Vol.945-946, p.233-239
Main Authors: Lin, Ying, Dong, Yuan, Chen, Jia, Li, Chun-Zheng, Nie, Zhi-Yong, Guo, Lei, Liu, Qin, Xie, Jian-Wei
Format: Article
Language:English
Subjects:
Administration, Cutaneous
Animals
Chemical Warfare Agents - metabolism
Gas Chromatography-Mass Spectrometry - methods
Gas chromatography–tandem mass spectrometry
Glutathione - metabolism
Lyases - metabolism
Male
Mustard Gas - administration & dosage
Mustard Gas - metabolism
Rabbit cutaneous exposure model
Rabbits
Sulfur mustard
Tandem Mass Spectrometry - methods
Urinalysis - methods
Urine
β-Lyase metabolites
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•A sensitive GC–MS/MS method was established and validated for quantitation of β-lyase metabolites of sulfur mustard.•SPE clean-up procedure was optimized in particular to yield high recoveries and very clean extracts.•The method was applied in a rabbit cutaneous exposure model for the first time.•The β-lyase metabolites of SM could be detected in urine from rabbits for up to 3 or 4 weeks after SM cutaneous exposure. A method for quantitation of β-lyase metabolites of sulfur mustard (SM) adducts with glutathione has been developed and validated using gas chromatography–tandem mass spectrometry (GC–MS/MS). The linear range of quantitation was 0.1–1000ng/mL in urine with a method detection limit of 0.02ng/mL. The method was applied in a rabbit exposure model. Domestic rabbits were cutaneously exposed to neat liquid SM in three dosage levels, and the β-lyase metabolites in urine were determined as 1,1′-sulfonylbis[2-(methylthio)ethane] (SBMTE). The study showed that even though more than 99% of the total amount of β-lyase metabolites was excreted in the first week after exposure, the β-lyase metabolites of SM adducts with glutathione could be detected in urine from rabbits for up to 3 or 4 weeks after the SM cutaneous exposure. For high dosage group (15mg/kg, 0.15 LD50), the mean concentration of SBMTE detected was 0.32ng/mL on day 28. For middle (5mg/kg, 0.05 LD50) and low (2mg/kg, 0.02 LD50) dosage groups, the mean concentrations of SBMTE were 0.07ng/mL and 0.02ng/mL on day 21, respectively. The data from this study indicate that the method is sensitive and provides a relatively long time frame for the retrospective detection of SM exposure.
ISSN:1570-0232
1873-376X
DOI:10.1016/j.jchromb.2013.11.058