期刊
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 26, 期 1, 页码 62-70出版社
ELSEVIER
DOI: 10.1016/j.ejps.2005.04.014
关键词
drug metabolism; metalloporphyrin; oxidation; chlorogenic acid; LC-MS-MS; mitochondria
Synthetic metalloporphyrins, in the presence of monooxygen donors, are known to mimic the various reactions of cytochrome P450 enzymes systems in the oxidation and oxygenation of various drugs and biologically active compounds. This paper reports an HPLC-MS-MS investigation of chlorogenic acid (CGA) oxidation by iodosylbenzene using iron(III) tetraphenylporphyrin chloride as catalyst. The oxidation products have been detected by sequential MS analyses. In addition, CGA was submitted to an in vitro metabolism assay employing isolated rat liver mitochondria. The single oxidized product obtained from mitochondrial metabolism corresponds to the major product formed by the metalloporphyrin-catalyzed reaction. These results indicate that biomimetic oxidation reactions, in addition to in vitro metabolism assays employing isolated organs/organelles, could replace some in vivo metabolism studies, thus minimizing the problems related to the use of a large number of living animals in experimental research. (c) 2005 Elsevier B.V. All rights reserved.
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