title: Identification of a major metabolite of danshensu in rat urine and simultaneous determination of danshensu and its metabolite in plasma: application to a pharmacokinetic study in rats.
abstract: Danshensu, as the effective component of Salvia miltiorrhiza (Danshen), has been widely used in clinical studies for treatment of cardiovascular diseases in China. A new metabolite, 4-hydroxy-3-methoxyphenyllactic acid was isolated from the urine of rats, and its chemical structure was identified by ultraviolet (UV), Infrared Spectroscopy (IR), mass spectrometry (MS) and nuclear magnetic resonance (NMR). Furthermore, a selective and sensitive high performance liquid chromatography-tandem mass spectrometric (HPLC-MS/MS) method was developed for the simultaneous quantification of danshensu and its major metabolite, 4-hydroxy-3-methoxyphenyllactic acid, in rat plasma after oral and intravenous administration of danshensu. The separation was performed on a Hypersil Gold C18 column (150 × 2.1 mm i.d., 3.0 µm, Thermo, San jose CA, USA) with gradient elution using a mobile phase composed of methanol and water (containing 0.1% formic acid) at a flow rate of 0.2 mL/min. Linear detection responses were obtained for danshensu and 4-hydroxy-3-methoxyphenyllactic acid ranging from 5 to 10000 ng/mL and 5 to 4000 ng/mL, respectively. The lower limits of quantification (LLOQs) for the two compounds were both 5 ng/mL. The intra-and inter-day precision (R.S.D %) were within 5.61% for the two analytes. The average recoveries of the analytes were greater than 72.43%. The method was proved to be stable during all sample storage, preparation and analytic procedures. This method was successfully applied to the pharmacokinetic studies of danshensu and 4-hydroxy-3-methoxyphenyllactic acid after oral and intravenous administration of danshensu in rats.
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Tianjin, 300410, China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Tianjin, 300410, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Tianjin, 300410, China.|School of Pharmaceutical Science and Technology, Tianjin University, 300072, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Ma
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Tianjin, 300410, China.
authors.forename: Kaijing
authors.initials: K
authors.lastname: Yan
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Tianjin, 300410, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Tianjin, 300410, China.
authors.forename: Min
authors.initials: M
authors.lastname: Han
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Tianjin, 300410, China.
authors.forename: Shuming
authors.initials: S
authors.lastname: Li
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Tianjin, 300410, China.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Tianjin, 300410, China.
authors.forename: Shuiping
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Tianjin, 300410, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Tianjin, 300410, China.
authors.forename: He
authors.initials: H
authors.lastname: Sun
authors.affiliation: Tianjin State key Laboratory of Pharmacokinetics and Pharmacodynamics, Tianjin Institute of Pharmaceutical Research, Tianjin, 300193, China.
authors.forename: Changxiao
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007773:Lactates / Q000032:analysis / Q000097:blood* / Q000378:metabolism / Q000652:urine*; D057230:Limit of Detection; D008297:Male; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D007773:Lactates; C035055:3,4-dihydroxyphenyllactic acid
keywords: 4-hydroxy-3-methoxyphenyllactic acid; danshensu; identification; metabolites; pharmacokinetics