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Quantitation of DNA reactive pyrrolic metabolites of senecionine – A carcinogenic pyrrolizidine alkaloid by LC/MS/MS analysis
Author(s) -
Qingsu Xia,
Xiaobo He,
Qiang Shi,
Ge Lin,
Peter P. Fu
Publication year - 2019
Publication title -
journal of food and drug analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.277
H-Index - 54
eISSN - 2224-6614
pISSN - 1021-9498
DOI - 10.1016/j.jfda.2019.12.001
Subject(s) - pyrrolizidine , pyrrolizidine alkaloid , carcinogen , chemistry , biochemistry , glutathione , microsome , alkaloid , metabolism , stereochemistry , in vitro , enzyme
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.

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