Isotope dilution LC/ESI--MS-MS quantitation of urinary 1,4-bis(N-acetyl-S-cysteinyl)-2-butanone in mice and rats as the biomarker of 1-chloro-2-hydroxy-3-butene, an in vitro metabolite of 1,3-butadiene.

Isotope dilution LC/ESI--MS-MS quantitation of urinary 1,4-bis(N-acetyl-S-cysteinyl)-2-butanone in mice and rats as the biomarker of 1-chloro-2-hydroxy-3-butene, an in vitro metabolite of 1,3-butadiene. Chem Biol Interact. 2019 Sep 25;311:108760 Authors: Wu WJ, Tang WF, Xiang MH, Yan J, Cao X, Zhou CH, Chang Y, Xi J, Cao YY, Luan Y, Zhang XY Abstract 1-Chloro-2-hydroxy-3-butene (CHB) is a possible metabolite of 1,3-butadiene, a carcinogenic air pollutant. To demonstrate its formation in vivo, it is desirable to develop a practical biomarker and the corresponding analysis method. CHB can undergo alcohol dehydrogenase- and cytochromes P450 enzymes (P450)-mediated oxidation to yield 1-chloro-3-buten-2-one (CBO), which readily forms glutathione conjugates. We hypothesized that CBO-derived mercapturic acids, which are the expected biotransformed products of CBO-glutathione conjugates, could be used as CHB biomarkers. Thus, in the present study, we investigated the in vivo biotransformation of CHB into CBO-derived mercapturic acids. Because the reaction of CBO with N-acetyl-l-cysteine yields two products, 1,4-bis(N-acetyl-S-cysteinyl)-2-butanone (NC1) and 1-chloro-4-(N-acetyl-S-cysteinyl)-2-butanone (NC2), we first developed an isotope dilution LC/ESI--MS-MS method to quantitate urinary NC1 and NC2, and then determined their concentrations in urine of C57BL/6 mice and Sprague-Dawley rats administered CHB. Since no NC2 was detected in sampl...
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Tags: Chem Biol Interact Source Type: research