title: Biotransformation of isoimperatorin by rat liver microsomes and its quantification by LC-MS/MS method.
abstract: The aim of the present research was to establish a comprehensive strategy to identify the metabolites of isoimperatorin after biotransformation with rat liver microsomes in vitro, and further describe metabolic kinetic characteristics of isoimperatorin and its main metabolites. Utilizing liquid chromatography with time of flight mass spectrometry (LC-TOF-MS), 18 metabolites (M 1-18) were characterized according to the typical fragment ions and literature data. Among them, M-2, 3, 5, 9, 10, and 15 were new compounds. To further verify structures of the metabolites, five main metabolites were obtained from the magnifying biotransformation incubation system, and their chemical structures were elucidated as 8-hydroxyoxypeucedanin (M-3), hydroxypeucedanin hydrate (M-4), E-5-(4-hydroxy-3-methyl-2-alkenyloxy)-psoralen (M-11), Z-5-(4-hydroxy-3-methyl-2-alkenyloxy)-psoralen (M-12), and oxypeucedanin (M-16) by various spectroscopy methods including IR, MS and NMR. A simple new liquid chromatography with triple quadrupole tandem mass spectrometry (LC-QqQ-MS) method was developed for the simultaneous determination of isoimperatorin and its main metabolites. The analysis was performed on a Diamonsil™ ODS C18 column with acetonitrile-water containing 0.1% formic acid as mobile phase. Total run time was 20.0 min. The results suggested that the method we exhibited was successfully applied for analysis of isoimperatorin and its metabolites. The study provides essential data for proposing metabolite pathway and further pharmacological study of isoimperatorin.
authors.affiliation: School of Pharmaceutical Sciences, Liaoning University of Traditional Chinese Medicine, Liaoning 116600, PR China; State Key Laboratory of Natural and Biomimetic Drugs (Peking University), Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, PR China. Electronic address: 731116920@qq.com.
authors.forename: Tian-Li
authors.initials: TL
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs (Peking University), Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, PR China.
authors.forename: You-Bo
authors.initials: YB
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs (Peking University), Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: School of Pharmaceutical Sciences, Liaoning University of Traditional Chinese Medicine, Liaoning 116600, PR China. Electronic address: kangtg@lnutcm.edu.cn.
authors.forename: Ting-Guo
authors.initials: TG
authors.lastname: Kang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs (Peking University), Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, PR China. Electronic address: xwyang@bjmu.edu.cn.
authors.forename: Xiu-Wei
authors.initials: XW
authors.lastname: Yang
mesh_terms: D029969:Angelica / Q000737:chemistry; D000818:Animals; D001711:Biotransformation; D002853:Chromatography, Liquid; D011564:Furocoumarins / Q000302:isolation & purification / Q000378:metabolism* / Q000493:pharmacokinetics; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism; D010936:Plant Extracts / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011564:Furocoumarins; D010936:Plant Extracts; C055542:isoimperatorin
keywords: Isoimperatorin; LC–QqQ–MS; Metabolism; Qualitative analysis; Quantitative analysis; Rat liver microsomes