益气活血固肾颗粒中5种有效成分在大鼠体内的药动学及组织分布研究
Pharmacokinetics and tissue distribution of five active components from Yiqi Huoxue Gushen Granules in rats
张雅净 1周美文 1林少敏 1王子苗 1全世建1
作者信息
- 1. 广州中医药大学中药学院,广东广州 510006
- 折叠
摘要
目的 探究益气活血固肾颗粒中巴马汀、药根碱、小檗碱、表小檗碱、芒柄花素在大鼠体内的药动学特征及组织分布规律,为进一步阐明该方的药效物质基础提供依据.方法 建立HPLC-MS/MS法测定大鼠口服给药4.75 g/kg益气活血固肾颗粒后血浆及各组织中的药物浓度,色谱柱选择Kromasil C18柱(3.5 μm,2.1 mm × 100 mm),流动相为乙腈-0.1％甲酸水溶液,流速为0.3 mL/min,进样量5 μL,采用电喷雾电离源(ESI)分别在正、负离子多反应监测模式(MRM)下进行扫描,选择WinNonlin 3.3软件计算主要药动学参数.结果 所建立的分析方法符合生物样品的检测要求,给予复方灌胃药液后,5种成分均可快速吸收入血,在30 min内血药浓度达到高峰,且药物在体内半衰期较短,消除速率快.各成分的达峰浓度Cmax、药时曲线下面积AUC0-t分别为4.87～233.12 μg/L、16.11～493.13 h/(μg·L).组织分布结果显示,5种成分在体内分布迅速且广泛,具有不均衡的特征,在胃和小肠中分布较多,其次是肝、肾、肺等组织,而在脾脏、心脏中分布较少.结论 该方法稳定、可靠,为复方益气活血固肾颗粒临床应用提供了参考.
Abstract
Objective To investigate the pharmacokinetics and tissue distribution of palmatine,jatrorrhizine,berberine,epiber-berine and formononetin of Yiqi Huoxue Gushen Granules(YHGG)in rats.To provide evidence for further clarifing the pharma-codynamic material basis of this prescription.Methods The HPLC-MS/MS method was established to detect the drug concentra-tion in rat plasma and tissues after oral administration of 4.75 g/kg YHGG.A Kromasil C18 column(3.5 μm,2.1 mm × 100 mm)as the stationary phase and the mobile phase consisted of acetonitrile-0.1％formic acid in water at the flow rate of 0.3 mL/min,the injection volume was 5 μL.The electrospray ionization source(ESI)was set in positive and negative ion mode re-spectively by multiple reaction monitoring(MRM)scanning.The main pharmacokinetic parameters were calculated by WinNonlin 3.3 software.Results The method met the detection requirements of biological samples.After intragastric administration of com-pound YHGG,the five components absorbed into the blood rapidly and the plasma concentrations can reached the peak within 30 min.Furthermore,all components owned short half-life and quick elimination rate in vivo.The Cmax and AUC0-t of each component were 4.87～233.12 μg/L,16.11～493.13 h/(μg·L),respectively.The results of tissue distribution showed that 5 components distributed rapidly,widely but unevenly in vivo.They were more distributed in the stomach and small intestine,fol-lowed by liver,kidney and lung,and less in the spleen and heart.Conclusion The method was stable and reliable which will provide reference for the clinical application of YHGG.
关键词
复方益气活血固肾颗粒/药动学/组织分布/高效液相色谱-串联质谱Key words
Compound Yiqi Huoxue Gushen Granules/Pharmacokinetics/Tissue distribution/HPLC-MS/MS引用本文复制引用
基金项目
广东省自然科学基金(2023A1515010843)
出版年
2024
NETL
NSTL
万方数据