Pharmacokinetic study of five ginsenosides using a sensitive and rapid liquid chromatography-tandem mass spectrometry method following single and multiple oral administration of Shexiang Baoxin pills to rats
Pharmacokinetic study of five ginsenosides using a sensitive and rapid liquid chromatography-tandem mass spectrometry method following single and multiple oral administration of Shexiang Baoxin pills to rats
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灵敏快速液相色谱-串联质谱法研究大鼠单次和多次口服麝香保心丸后五种人参皂苷的药代动力学
DOI：
10.1002/bmc.3293
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发表时间：
2015-03-01
影响因子：
1.8
通讯作者：
Zhang, Weidong
中科院分区：
文献类型：
--
作者：
Peng, Chengcheng;Yang, Yongge;Zhang, Weidong
麝香保心丸（SBP）是一种用于治疗冠心病的中药。人参皂苷是SBP的主要有效成分，但对人参皂苷在SBP中的药代动力学（包括多次给药和线性或非线性特性）缺乏全面、深入的研究。本研究旨在研究和比较人参皂苷在 SBP 中单剂量和多剂量的药代动力学特征。建立了同时测定大鼠血浆中人参皂苷Rg1、Re、Rb3、Rc和Rb1的液相色谱-串联质谱(LC-MS/MS)方法。大鼠被随机分配接受单剂量 4、8 或 12 g/kg 和连续 8、15 或 22 天的多剂量 (4 g/kg) SBP。结果显示，单次口服剂量 4 或 8 g/kg 后，人参皂苷被迅速吸收，T-max 范围为 0.250 至 1.08 小时。 ppd型人参皂苷Rb3、Rc和Rb1的AUC(0-t)和C-max大于ppt型人参皂苷Rg1和Re。所有人参皂苷在 4-12 g/kg 剂量下均观察到非剂量依赖性暴露。多次给药后，ppt型人参皂苷的血浆水平下降，而ppd型人参皂苷的血浆水平没有显着变化。总之，LC-MS/MS 方法成功应用于研究单次和多次口服 SBP 后人参皂苷的药代动力学。多次给药后人参皂苷没有蓄积。与ppt型人参皂苷相比，ppd型人参皂苷表现出更有利的药代动力学特性。版权所有 (c) 2014 约翰·威利父子有限公司
Shexiang Baoxin pills (SBP) are a traditional Chinese medicine that are used for treating coronary heart disease. Ginsenosides are the main effective components of SBP, but a comprehensive and deep pharmacokinetic study of ginsenosides in SBP, including multiple dosing and linear or nonlinear properties, is lacking. This study was designed to investigate and compare the pharmacokinetic characteristics of ginsenosides in SBP at a single dose and in multiple doses. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of the ginsenosides Rg1, Re, Rb3, Rc and Rb1 in rat plasma. Rats were randomly assigned to receive a single dose of 4, 8 or 12 g/kg and multiple doses (4 g/kg) of SBP for 8, 15 or 22 consecutive days. The results revealed that ginsenosides, following a single oral dose of 4 or 8 g/kg, were absorbed rapidly, with a T-max ranging from 0.250 to 1.08 h. The AUC(0-t) and C-max of the ppd-type ginsenosides Rb3, Rc and Rb1 were greater than those of the ppt-type ginsenosides Rg1 and Re. Nondose-dependent exposure was observed at doses of 4-12 g/kg for all of the ginsenosides. After multiple dosing, the plasma levels of the ppt-type ginsenosides decreased, whereas those of the ppd-type ginsenosides did not change significantly. In conclusion, the LC-MS/MS method was successfully applied to investigate the pharmacokinetics of ginsenosides after single and multiple oral administrations of SBP. The ginsenosides did not accumulate after multiple dosing. The ppd-type ginsenosides displayed more favorable pharmacokinetic properties compared with the ppt-type ginsenosides. Copyright (c) 2014 John Wiley & Sons, Ltd.