https://scholars.lib.ntu.edu.tw/handle/123456789/630656
標題: | Simultaneous detection of the tetrachloroethylene metabolites S-(1,2,2-trichlorovinyl) glutathione, S-(1,2,2-trichlorovinyl)-L-cysteine, and N-acetyl-S-(1,2,2-trichlorovinyl)-L-cysteine in multiple mouse tissues via ultra-high performance liquid chromatography electrospray ionization tandem mass spectrometry | 作者: | YU-SYUAN LUO Cichocki, Joseph A McDonald, Thomas J Rusyn, Ivan |
關鍵字: | DEPENDENT DIFFERENCES; TRICHLOROETHYLENE METABOLISM; TRICHLOROACETIC-ACID; DICHLOROACETIC ACID; MERCAPTURIC ACID; L-CYSTEINE; AMES TEST; PERCHLOROETHYLENE; MICE; TOXICITY | 公開日期: | 2017 | 出版社: | TAYLOR & FRANCIS INC | 卷: | 80 | 期: | 9 | 起(迄)頁: | 513 | 來源出版物: | Journal of toxicology and environmental health. Part A | 摘要: | Tetrachloroethylene (perchloroethylene; PERC) is a high-production volume chemical and ubiquitous environmental contaminant that is hazardous to human health. Toxicity attributed to PERC is mediated through oxidative and glutathione (GSH) conjugation metabolites. The conjugation of PERC by glutathione-s-transferase to generate S-(1,2,2-trichlorovinyl) glutathione (TCVG), which is subsequently metabolized to form S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC) is of special importance to human health. Specifically, TCVC may be metabolized to N-acetyl-S-(1,2,2-trichlorovinyl)-L-cysteine (NAcTCVC) which is excreted through urine, or to electrophilic metabolites that are nephrotoxic and mutagenic. Little is known regarding toxicokinetics of TCVG, TCVC, and NAcTCVC as analytical methods for simultaneous determination of these metabolites in tissues have not yet been reported. Hence, an ultra-high-performance liquid chromatography electrospray ionization tandem mass spectrometry-based method was developed for analysis of TCVG, TCVC, and NAcTCVC in liver, kidneys, serum, and urine. The method is rapid, sensitive, robust, and selective for detection all three analytes in every tissue examined, with limits of detection (LOD) ranging from 1.8 to 68.2 femtomoles on column, depending on the analyte and tissue matrix. This method was applied to quantify levels of TCVG, TCVC, and NAcTCVC in tissues from mice treated with PERC (10 to 1000 mg/kg, orally) with limits of quantitation (LOQ) of 1-2.5 pmol/g in liver, 1-10 pmol/g in kidney, 1-2.5 pmol/ml in serum, and 2.5-5 pmol/ml in urine. This method is useful for further characterization of the GSH conjugative pathway of PERC in vivo and improved understanding of PERC toxicity. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/630656 | ISSN: | 1528-7394 | DOI: | 10.1080/15287394.2017.1330585 |
顯示於: | 食品安全與健康研究所 |
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