title: 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.
abstract: 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.
authors.affiliation: Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, 100850 Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, 100850 Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, 100850 Beijing, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, 100850 Beijing, China.
authors.forename: Chun-Zheng
authors.initials: CZ
authors.lastname: Li
authors.affiliation: Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, 100850 Beijing, China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Nie
authors.affiliation: Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, 100850 Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, 100850 Beijing, China. Electronic address: liuq920@126.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, 100850 Beijing, China. Electronic address: xiejw@bmi.ac.cn.
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Xie
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002619:Chemical Warfare Agents / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D005978:Glutathione / Q000378:metabolism*; D008190:Lyases / Q000378:metabolism*; D008297:Male; D009151:Mustard Gas / Q000008:administration & dosage / Q000378:metabolism*; D011817:Rabbits; D053719:Tandem Mass Spectrometry / Q000379:methods*; D016482:Urinalysis / Q000379:methods
chemical_list: D002619:Chemical Warfare Agents; D008190:Lyases; D005978:Glutathione; D009151:Mustard Gas
keywords: Gas chromatography–tandem mass spectrometry; Rabbit cutaneous exposure model; Sulfur mustard; Urine; β-Lyase metabolites