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

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Abstract

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.

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Authors and Affiliations

  1. Research Institute of Hygiene, Occupational Pathology, and Human Ecology, Federal Medical and Biological Agency of Russia, 188663, Kuzmolovsky, Leningrad oblast, Russia

    O. I. Orlova, G. V. Karakashev & E. I. Savel’eva

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  1. O. I. Orlova
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  2. G. V. Karakashev
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  3. E. I. Savel’eva
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Correspondence to O. I. Orlova.

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Conflict of interests. The authors declare that they have no conflict of interest.

Statement on the welfare of animals. The working conditions with experimental animals were under the “Rules of Laboratory Practice in the Russian Federation (GLP)” approved by the Order of the Ministry of Health of the Russian Federation on June 19, 2003, no. 267.

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Translated by O. Zhukova

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Orlova, O.I., Karakashev, G.V. & Savel’eva, E.I. Simultaneous Determination of Sulfur Mustard Adducts with Guanine and Acetylcysteine in Urine by High-Resolution High-Performance Liquid Chromatography–Tandem Mass Spectrometry. J Anal Chem 75, 1011–1017 (2020). https://doi.org/10.1134/S1061934820060155

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