title: Identification of metabolites of honokiol in rat urine using 13C stable isotope labeling and liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry.
abstract: A general approach based on stable isotope labeling and UPLC/Q-TOF-MS analysis of in vivo novel metabolites of honokiol has been developed in our study. In this method, urine samples were collected after intravenous administration of mixture of regular and [(13)C6]-labeled honokiol at 1:1 ratio to healthy rats. The metabolites could be easily recognized by the determination of a chromatographically co-eluted pair of isotopomers (MS doublet peaks) with similar peak intensities and mass difference corresponding to that between isotope-labeled and non-isotope-labeled honokiol. A total of 51 metabolites were detected, 37 of which were tentatively identified based on mass accuracy (<5 ppm). Among them, 33 of honokiol metabolites were first reported with 5 metabolites belonging to phase I and other 32 metabolites belonging to phase II metabolites. Our results highlighted that the main phase I metabolic pathways of honokiol in rats were oxidation, and the phase II metabolic pathways were sulfation, glucuronidation, acetylation as well as amino acids conjugation. This was the first research focused on the biotransformation of honokiol in rats, and the identification of these metabolites might provide us essential information for further pharmacological and clinical studies of honokiol.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610065, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Minghai
authors.initials: M
authors.lastname: Tang
authors.forename: Huijun
authors.initials: H
authors.lastname: Lai
authors.forename: Yinfeng
authors.initials: Y
authors.lastname: Dong
authors.forename: Caifeng
authors.initials: C
authors.lastname: Xie
authors.forename: Haoyu
authors.initials: H
authors.lastname: Ye
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.forename: Neng
authors.initials: N
authors.lastname: Qiu
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Li
authors.forename: Lulu
authors.initials: L
authors.lastname: Cai
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D001711:Biotransformation; D001713:Biphenyl Compounds / Q000737:chemistry* / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000378:metabolism; D007553:Isotope Labeling; D017705:Lignans / Q000737:chemistry* / Q000378:metabolism; D031566:Magnolia / Q000737:chemistry*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D004365:Drugs, Chinese Herbal; D017705:Lignans; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols