Предложена методика определения биомаркера воздей ствия сернистого иприта-его аддукта с ДНК, N7-[2-[(2-гидроксиэтил)-тио]-этил]-гуанина (N7-HETEG), методом ВЭЖХ-МС/МС с электрораспылительной ионизацией. Для разработки методики был синтезирован и очищен аналитический стандарт с содержанием основного вещества не менее 90%. Достигнутый предел определения методики составляет 5 нг/мл. Построены градуировочные зависимости содержания аддукта в линейном диапазоне 1-100 нг/мл. Методика апробирована при анализе образцов мочи крыс, экспонированных сернистым ипритом в нелетальной дозе (2 мг/кг). Библиогр. 13 назв. Ил. 10. Табл. 1.
A procedure for determination of the lewisite metabolite 2-chlorovinylarsonous acid (CVAA) in biomedical samples, involving derivatization of the latter with propane-1,3-dithiol and head-space solid-phase microextraction of the derivative on a 100-μm PDMS fiber followed by GC-MS, was applied for the first time to analysis ofin vivosamples. The detection limits of CVAA in urine, plasma and red blood cells were 0.1, 1.0 and 10 ng/ml, respectively. Upon exposure to lewisite at a dose of 1.6 mg/kg, CVAA could be detected in rat urine for about three months. Study of the effect of a single injection of the antidote unithiol on the CVAA excretion profile revealed more active CVAA excretion during the first two days after the injection, compared to that observed in the absence of antidotal therapy.
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