Simultaneous Determination of Sulfur Mustard Adducts with Guanine and Acetylcysteine in Urine by High-Resolution High-Performance Liquid Chromatography–Tandem Mass Spectrometry

• Published in: Journal of analytical chemistry (New York, N.Y.) Vol. 75; no. 8; pp. 1011 - 1017
• Main Authors: Orlova, O. I., Karakashev, G. V., Savel’eva, E. I.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01-08-2020; Springer; Springer Nature B.V
• Subjects: Acetylcysteine; Adducts; Analysis; Analytical Chemistry; Antidotes; Biomarkers; Chemistry; Chemistry and Materials Science; Ethane; Guanine; High performance liquid chromatography; High resolution; Ions; Mass spectrometry; Mustard gas; Poisoning; Reaction kinetics; Scientific imaging; Spectroscopy; Sulfides; Sulfur; Urine; Russia; HPLC–tandem mass spectrometry; acetylcysteine; bioassays; metabolite; adduct; DNA; scavenger; biomarker; sulfur mustard
• ISSN: 1061-9348; 1608-3199
• DOI: 10.1134/S1061934820060155

We propose a procedure for the simultaneous determination of biomarkers of the action of sulfur mustard (SM, 2,2'-dichlorodiethyl sulfide), namely, a depurinized adduct with DNA (N7-hydroxyethylthioethyl guanine) and an adduct with acetylcysteine (ACC) (1,1'-sulfonylbis[2-
S
-(
N
-acetylcysteinyl)ethane]), in urine by high-resolution HPLC–tandem mass spectrometry with electrospray ionization. The limit of quantification reached for both analytes is 10 ng/mL. The calibration plots are linear in the range 10–200 ng/mL. The procedure was tested in the analysis of urine samples obtained after the subcutaneous administration of sulfur mustard to rats in nonlethal dose (2 mg/kg) both in the absence of therapy and in using ACC as a scavenger (antidote). The positive effect of ACC therapy on the kinetics of sulfur mustard excretion from a body in the first hours after poisoning was found at the molecular level for the first time, and the protective effect of ACC on DNA in case of damage with sulfur mustard was substantiated.