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 |
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| Authors: | Xiangyang Wang Wei Li Xiaohui Ma Kaijing Yan Yang Chu Min Han Shuming Li Hongchao Zhang Shuiping Zhou Yonghong Zhu He Sun Changxiao Liu |
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| Affiliation: | 1. Tasly R&D Institute, Tianjin Tasly Group Co., Ltd., Tianjin, China;2. School of Pharmaceutical Science and Technology, Tianjin University, China;3. Tianjin State key Laboratory of Pharmacokinetics and Pharmacodynamics, Tianjin Institute of Pharmaceutical Research, Tianjin, China |
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| 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.Copyright © 2014 John Wiley & Sons, Ltd. |
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| Keywords: | danshensu 4‐hydroxy‐3‐methoxyphenyllactic acid identification metabolites pharmacokinetics |
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