怀牛膝“性善下行”对通塞脉微丸中绿原酸、异甘草苷、哈巴俄苷和甘草素体内药代动力学影响研究

Studies on effects of Achyranthes bidentata on Tongsaimai pellets main active ingredients chlorogenic acid,isoliquiritin,harpagoside and glycyrrhizin in vivo pharmacokinetics

为了探索怀牛膝对通塞脉微丸中主要活性成分绿原酸、异甘草苷、哈巴俄苷和甘草素在大鼠体内的药动学参数的影响,该研究建立了UPLC-MS/MS同时测定大鼠血浆中绿原酸、异甘草苷、哈巴俄苷和甘草素4种成分的分析方法,色谱柱为BEHC18(2.1 mm×100 mm,1.7μm);流动相为乙腈-0.1%甲酸水梯度洗脱,流速为0.3 mL·min-1,采用电喷雾电离源(ESI),多反应离子监测(MRM)扫描方式。结果显示,通塞脉微丸组4种成分的Cmax和AUC0-∞均比通塞脉微丸加牛膝组高,其中绿原酸的Cmax差异显著(P<0.05),绿原酸和甘草素的AUC0-∞差异显著(P<0.05);2组间Tmax和CL均无显著性差异。该研究建立的UPLC-MS/MS方法特异、快速、准确和灵敏,可用于通塞脉微丸中4种主要活性成分在大鼠体内的药代动力学研究;同时表明怀牛膝对通塞脉微丸中4种主要活性成分在大鼠体内药代动力学行为有不同程度的影响。

To study on the effects of Achyranthes bidentata on Tongsaimai pellets main active ingredients chlorogenic acid, isoliqniritin, harpagoside and glycyrrhizin in rats in vivo pharmacokinetic behaviors, a method for the simultaneous determination of chlorogenic acid, isoliquiritin, harpagoside and liquiritigenin in rat plasma was established by UPLC-MS/MS. The analysis was per- formed on a waters Acquity BEH C18 column（2. 1 mm × 100 mm, 1.7 μm）with the mixture of acetonitrile and 0. 1% formic acid/water as mobile phase, and the gradient elution at a flow rate of 0. 3 mL min- 1. The analytes were detected by tandem mass spectrometry with the electrospray ionization（ ESI） source and in the muhiple reaction monitoring（MRM） mode. It turned out that the analytes of Tongsaimai pellets groups Cmax and AUC0-∞ values were higher than that with A. bidentata group, and the Cmax values of chlorogenic acid had significantly difference（P 〈 0. 05）, the AUC0-∞ values of chlorogenic acid and glycyrrhizin had significantly difference （P 〈 0. 05） ; The Tmax and CL values of two groups had no significantly difference. Results showed that the established method was specific, rapid, accurate and sensitive for the studies of Tongsaimai pellets four main active ingredients in rat in vivo pharmacokinetic, and A. bidentata have varying degrees.of effects on Tongsaimai pellets four main active ingredients in rat in vivo pharmacokinetic behaviors.