title: The metabolism of YiGan San and subsequent pharmacokinetic evaluation of four metabolites in rat based on liquid chromatography with tandem mass spectrometry.
abstract: A new method based on liquid chromatography-tandem time-of-flight mass spectrometry was developed to identify the metabolites in rat urine after oral administration of YiGan San (YGS). Eighteen prototype compounds and four metabolites named 11-hydroxyhirsuteine, 19-carbonylhirsutine, 19-carbonyl-dihydrocorynantheine, and 18-hydroxy-geissoschizine methyl ether were identified. Subsequently, a method of high-performance liquid chromatography coupled with triple-quadrupole mass spectrometry was established for pharmacokinetic study of YGS in rat plasma. The concentration-time curves of four prototype compounds, senkyunolide I, ajmalicine, isocorynoxeine and rhynchophylline were constructed after an oral (9.1g YGS per kilogram of body weight) administration in rats. Method validation revealed excellent linearity over the range 220.00-0.55, 220.00-0.55, 21.40-0.05, and 19.80-0.05ng/mL for the four prototype compounds respectively. The stabilities results indicate that all of the analytes were stable in rat plasma in the autosampler for 24h, under freeze/thaw cycles (4 times in 24h), and at -20°C for one week. Residual analysis, heteroskedasticity test, and goodness-of-fit test were also performed to determine the accuracy of the linear regression method. The pharmacokinetic parameters were obtained. Four hours after administration, compound 11-hydroxyhirsuteine can be detected in rat plasma. Compared with purified ligustilide, YGS required a slightly longer period to reach maximum concentration (Cmax) in rat plasma.
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; The Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Gai
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, China. Electronic address: liuwenyuan8506@163.com.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: fengsunlight@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Feng
authors.affiliation: Jiangxi Qingfeng Pharmaceutical Corporation, Ganzhou, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Xie
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000032:analysis* / Q000493:pharmacokinetics; D026121:Indole Alkaloids / Q000652:urine; D008297:Male; D000078183:Oxindoles; D051381:Rats; D017207:Rats, Sprague-Dawley; D046948:Secologanin Tryptamine Alkaloids / Q000652:urine; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D001572:Benzofurans; D004365:Drugs, Chinese Herbal; D026121:Indole Alkaloids; D000078183:Oxindoles; D046948:Secologanin Tryptamine Alkaloids; C524644:Yi-Gan San; C576743:senkyunolide I; C054799:corynoxeine; C052714:rhyncophylline; C005709:raubasine
keywords: High performance liquid chromatography; Metabolites; Pharmacokinetics; Quadrupole mass spectrometry; Time-of-flight mass spectrometry; YiGan San