title: Pharmacokinetic profile and metabolite identification of yuanhuapine, a bioactive component in Daphne genkwa by ultra-high performance liquid chromatography coupled with tandem mass spectrometry.
abstract: Daphne genkwa Sieb. et Zucc. (Thymelaeaceae) is mainly used for the treatment of edema, asthma, and cancer in China and Korea for centuries. The major bioactive components in D. genkwa are daphnane-type diterpenoids, which showed pharmacological activities such as antileukemic, antifertility and skin irritants. In this study, the pharmacokinetics and metabolism profile of yuanhuapine, an effective and toxic diterpenoid, was investigated in rats. The plasma exposure of yuanhuapine was determined by ultra-performance liquid chromatography tandem triple-quadrupole mass spectrometry (UPLC-TQ-MS), and the pharmacokinetic parameters were calculated using the DAS 2.0 pharmacokinetic program. The metabolites were identified through ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and a Metabolynx™ (v4.1) program. After oral administration (5 mg/kg), yuanhuapine was slowly absorbed and reached a maximum concentration of 579.20 ± 212.85 ng/mL at 7.33 ± 1.03 h, it also eliminated slowly. As the cumulative excretion of yuanhuapine in urine and feces were only 0.7% and 3.3%, we supposed that biotransformation in vivo was of significant importance to this component. Not only the prototype but also twelve metabolites were found and tentatively identified in rat urine after oral administration of yuanhuapine. The metabolic pathway mainly involves hydroxylation, methylation, glucuronidation and cysteine conjugation during the phase I and phase II biotransformation pathway. All the information gained here was useful in understanding the pharmacological actions and toxic properties of yuanhuapine, and providing a meaningful basis for clinical application of such a bioactive compound of herbal medicines.
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Guo
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wu
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Tao
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Yefei
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: dja@njutcm.edu.cn.
authors.forename: Jin-ao
authors.initials: JA
authors.lastname: Duan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D032364:Daphne / Q000737:chemistry*; D004224:Diterpenes / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D005243:Feces / Q000737:chemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D004224:Diterpenes; D004365:Drugs, Chinese Herbal; C512330:Yuanhuapine
keywords: LC–MS/MS; Metabolite identification; Pharmacokinetic profile; Yuanhuapine