Pyrrolizidine alkaloids (PAs) are carcinogenic phytochemicals, inducing liver tumors in experimental rodents. We previously determined that (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP), 7-glutathione-DHP, 7-cysteine-DHP, 7-N-acetylcysteine-DHP, and 1-CHO-DHP are DNA reactive pyrrolic metabolites potentially associated with PA-induced liver tumor initiation. In this study, we developed an LC/MS/MS multiple reaction monitoring (MRM) mode method to identify and quantify these metabolites formed from the metabolism of senecionine, a carcinogenic PA, by mouse, rat, and human liver microsomes, and primary rat hepatocytes. Together with the chemically prepared standards of these metabolites, this represents an accurate and convenient LC/MS/MS analytical method for quantifying these five reactive pyrrolic metabolites in biological systems.

中文翻译：

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通过 LC/MS/MS 分析对 senecionine 的 DNA 反应性吡咯代谢物进行定量——一种致癌的吡咯里西啶生物碱

吡咯里西啶生物碱 (PAs) 是致癌植物化学物质，可诱发实验啮齿动物的肝脏肿瘤。我们之前确定了 (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)、7-glutathione-DHP、7-cysteine-DHP、7-N-acetylcysteine-DHP 和1-CHO-DHP 是 DNA 反应性吡咯代谢物，可能与 PA 诱导的肝肿瘤发生有关。在本研究中，我们开发了一种 LC/MS/MS 多反应监测 (MRM) 模式方法来识别和量化这些代谢物，这些代谢物是由小鼠、大鼠和人肝微粒体以及原代大鼠的 senecionine（一种致癌 PA）代谢形成的。肝细胞。连同这些代谢物的化学制备标准，