title: Integrated identification, qualification and quantification strategy for pharmacokinetic profile study of Guizhi Fuling capsule in healthy volunteers.
abstract: Guizhi Fuling capsule (GZFL), a traditional Chinese medicine formulation, is widely used in China to relieve pain from dysmenorrhea and is now in a Phase II clinical trial in the USA. Due to the low exposure of the five main medicative ingredients (amygdalin, cinnamic acid, gallic acid, paeoniflorin and paeonol) of GZFL in human, a strategy was built to qualitatively and quantitatively identify the possible metabolites of GZFL and to describe the pharmacokinetic profiles of GZFL in human. In this strategy, LC-Q-TOF/MS was used to identify and structurally elucidate the possible metabolites of GZFL in vivo; and a time-based metabolite-confirming step (TBMCs) was used to confirm uncertain metabolites. The simultaneously quantitation results by LC-MS/MS showed low exposure of the five medicative ingredients. According to the strategy we built, a total of 36 metabolites were found and structurally elucidated. The simultaneously semi-quantitative analysis by LC-MS/MS showed that obvious time-concentration curves could be established for 12 of the metabolites, and most of them showed a relatively higher exposure. This study provides a better understanding of the metabolic processes of GZFL in human.
authors.affiliation: Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Yun-Xi
authors.initials: YX
authors.lastname: Zhong
authors.affiliation: Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Jin
authors.affiliation: Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Shi-Yin
authors.initials: SY
authors.lastname: Gu
authors.affiliation: Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: China Application Center, SCIEX, Beijing, China.
authors.forename: Ke-Rong
authors.initials: KR
authors.lastname: Zhang
authors.affiliation: Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Bing-Chen
authors.initials: BC
authors.lastname: Ou-Yang
authors.affiliation: Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Lab of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Pharmaceutical Co. Ltd, Lianyungang, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.affiliation: State Key Lab of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Pharmaceutical Co. Ltd, Lianyungang, Jiangsu, China.
authors.forename: Zhen-Zhong
authors.initials: ZZ
authors.lastname: Wang
authors.affiliation: Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Aa
authors.affiliation: Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Guang-Ji
authors.initials: GJ
authors.lastname: Wang
authors.affiliation: Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Sun
mesh_terms: D000098:Acetophenones / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000678:Amygdalin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D002214:Capsules; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002934:Cinnamates / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D005707:Gallic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005960:Glucosides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D015394:Molecular Structure; D039821:Monoterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods; D006027:Glycosides
chemical_list: D000098:Acetophenones; D000678:Amygdalin; D002214:Capsules; D002934:Cinnamates; D004365:Drugs, Chinese Herbal; D005707:Gallic Acid; D005960:Glucosides; D039821:Monoterpenes; C525079:guizhi-fuling; C029010:cinnamic acid; C015423:peoniflorin; D006027:Glycosides; C013638:paeonol