title: Stereoselective pharmacokinetic study of rhynchophylline and isorhynchophylline epimers in rat plasma by liquid chromatography-tandem mass spectrometry.
abstract: 1. In this study, the stereoselective pharmacokinetics of rhynchophylline (RIN) and isorhynchophylline (IRN) in rat plasma were investigated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). 2. A rapid, robust and sensitive LC-MS/MS method for simultaneous quantification of RIN and IRN in rat plasma was established and validated. Chromatographic separation was performed on a Poroshell 120 EC-C18column under a gradient elution with methanol and water containing 0.01% ammonia as mobile phase. Calibration curve was linear over a concentration range of 1-2000 ng/mL for both epimers. 3. After intravenous administration, there was no apparent difference in pharmacokinetic parameters between two epimers. However, after oral administration, RIN showed remarkable higher plasma exposure than IRN. The bioavailability, Cmaxand AUC0-tof RIN were about 9.2-fold, 6.4-fold and 9.1-fold higher than those of IRN at 10 mg/kg, and 7.8-fold, 4.3-fold and 7.7-fold at 20 mg/kg, respectively. Additionally, with dosage enhanced from 10 mg/kg to 20 mg/kg, the plasma concentrations of RIN or IRN increased significantly and the bioavailability enhanced about three times. 4. In conclusion, the results of this work demonstrated for the first time that the pharmacokinetics of RIN and IRN have stereoselectivity.
authors.affiliation: a Department of Pharmaceutical Analysis , China Pharmaceutical University , Nanjing , China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: a Department of Pharmaceutical Analysis , China Pharmaceutical University , Nanjing , China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zheng
authors.affiliation: b Pharmic Laboratory Animal Center, China Pharmaceutical University , Nanjing , China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: a Department of Pharmaceutical Analysis , China Pharmaceutical University , Nanjing , China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Qiao
authors.affiliation: a Department of Pharmaceutical Analysis , China Pharmaceutical University , Nanjing , China.|c Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University , Nanjing , China , and.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Liu
authors.affiliation: d Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University , Nanjing , China.
authors.forename: Feng
authors.initials: F
authors.lastname: Feng
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002853:Chromatography, Liquid; D026121:Indole Alkaloids / Q000493:pharmacokinetics*; D000078183:Oxindoles; D010949:Plasma / Q000378:metabolism*; D051381:Rats; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry
chemical_list: D026121:Indole Alkaloids; D000078183:Oxindoles; C052714:rhyncophylline
keywords: Epimers; LC–MS/MS; isorhynchophylline; rat plasma; rhynchophylline; stereoselective pharmacokinetics