title: Metabolism studies on prim-O-glucosylcimifugin and cimifugin in human liver microsomes by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry.
abstract: Prim-O-glucosylcimifugin (PGCN) and cimifugin (CN) are major constituents of Radix Saposhnikoviae that have antipyretic, analgesic and anti-inflammatory pharmacological activities. However, there were few reports with respect to the metabolism of PGCN and CN in vitro. In this paper, we describe a strategy using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) for fast analysis of the metabolic profile of PGCN and CN in human liver microsomes. In total, five phase I metabolites of PGCN, seven phase I metabolites and two phase II metabolites of CN were identified in the incubation of human liver microsomes. The results revealed that the main phase I metabolic pathways of PGCN were hydroxylation and hydrolysis reactions. The phase I metabolic pathways of CN were found to be hydroxylation, demethylation and dehydrogenation. Meanwhile, the results indicated that O-glucuronidation was the major metabolic pathway of CN in phase II metabolism. The specific UDP-glucuronosyltransferase (UGT) enzymes responsible for CN glucuronidation metabolites were identified using recombinant UGT enzymes. The results indicated that UGT1A1, UGT1A9, UGT2B4 and UGT2B7 might play major roles in the glucuronidation of CN. Overall, this study may be useful for the investigation of metabolic mechanism of PGCN and CN, and it can provide reference and evidence for further pharmacodynamic experiments. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, People's Republic of China.|Department of Pharmacy, Eye Hospital of Hebei Province, Xingtai, Hebei, People's Republic of China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Jia
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, People's Republic of China.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, People's Republic of China.
authors.forename: Qiaoyue
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, People's Republic of China.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, People's Republic of China.
authors.forename: Haotian
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, People's Republic of China.
authors.forename: He
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, People's Republic of China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, People's Republic of China.
authors.forename: Lantong
authors.initials: L
authors.lastname: Zhang
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D002867:Chromones / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D008862:Microsomes, Liver / Q000378:metabolism*; D009005:Monosaccharides / Q000378:metabolism*; D012015:Reference Standards; D014966:Xanthenes / Q000378:metabolism*
chemical_list: D002867:Chromones; D009005:Monosaccharides; D014966:Xanthenes; C533198:cimifugin; C498945:prim-O-glucosylcimifugin
keywords: Cimifugin; Human liver microsomes; Metabolism; Prim-O-glucosylcimifugin; UPLC-Q-TOF-MS