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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
Journal of Analytical Chemistry ( IF 1.0 ) Pub Date : 2020-07-31 , DOI: 10.1134/s1061934820060155
O. I. Orlova , G. V. Karakashev , E. I. Savel’eva

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.

中文翻译:

高效液相色谱-串联质谱法同时测定尿液中鸟嘌呤和乙酰半胱氨酸中的芥菜硫加合物

我们提出了一种同时测定芥菜(SM,2,2'-dichlorodiethyl sulfide)的作用的生物标志物的程序,即与DNA(N7-羟乙基硫乙基鸟嘌呤)的脱嘌呤加合物和与乙酰半胱氨酸(ACC)的加合物1,1'-磺酰基双[2- S-N-乙酰半胱氨酰)乙烷]),采用电喷雾电离的高分辨率HPLC-串联质谱法测定尿液中。两种分析物的定量极限均为10 ng / mL。校准图在10–200 ng / mL范围内是线性的。在无治疗和使用ACC作为清除剂(解毒剂)的情况下,以非致死剂量(2 mg / kg)对大鼠皮下施用硫芥末后获得的尿液样品的分析,对该程序进行了测试。首次在分子水平上发现了ACC治疗对中毒后头几小时芥菜从体内排泄动力学的积极影响,并证实了ACC对DNA的保护作用,以防芥子碱被破坏。 。
更新日期:2020-07-31
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