Journal of Food and Drug Analysis (JFDA)
【Update Date:2020-01-07】unit:
Quantitation of DNA reactive pyrrolic metabolites of senecionine – A carcinogenic pyrrolizidine alkaloid by LC/MS/MS analysis
Qingsu Xia a, Xiaobo He a, Qiang Shi a, Ge Lin b, Peter P. Fu a,*
a National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, United States
b School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
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.
Keywords: Pyrrolizidine alkaloid; Senecionine; Pyrrolic metabolites; Carcinogenicity; LC/MS/MS analysis
https://doi.org/10.1016/j.jfda.2019.12.001.
(http://www.sciencedirect.com/science/article/pii/S1021949819301036)