芪苈强心胶囊中酚酸类成分在大鼠体内药动学研究

Pharmacokinetic study of phenolic acids in rat plasma after oral administration of Qili Qiangxin Capsule

关键词:  芪苈强心胶囊  HPLC-MS/MS  酚酸  药动学

Key words:  Qili Qiangxin Capsule  HPLC-MS/MS  phenolic acids  pharmacokinetics

摘要:

[目的]建立高效液相色谱-串联质谱（HPLC-MS/MS）的方法，考察大鼠灌胃给药后，芪苈强心胶囊中酚酸类成分（丹酚酸A、丹酚酸B、丹参素、紫草酸、迷迭香酸、原儿茶酸）的药动学特征。[方法]采用Agilent ZOBRAX XDB-C₁₈色谱柱（4.6 mm×50 mm，3.5 μm），柱温40℃，流动相[0.1% 甲酸水溶液（A）]-[含0.1% 甲酸的乙腈溶液（B）]梯度洗脱，流速0.45 mL/min，进样量 10 μL；采用电喷雾离子源（ESI），多反应监测（MRM）负离子模式下测定血药浓度。[结果]方法学结果符合要求。大鼠灌胃芪苈强心胶囊后，血浆中6种酚酸类活性成分的达峰时间（T_max）在10~40 min内，半衰期（t_1/2）在3.34~8.38 h间；血药达峰浓度（C_max）和血药浓度-时间曲线下面积（AUC_0-∞）从大到小排序依次为丹酚酸B > 丹参素 > 紫草酸 > 迷迭香酸 > 原儿茶酸 > 丹酚酸A。[结论]该检测方法专属性强，重复性好，可用于芪苈强心胶囊中酚酸类成分的药动学研究。

Abstract:

[Objective] A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed to study the pharmacokinetic characteristics of phenolic acids (salvianolic acid A,salvianolic acid B,danshensu,lithospermic acid,rosmarinic acid,protocatechuic aldehyde) in rat plasma after oral administration of Qili Qiangxin Capsule.[Methods] An Agilent ZOBRAX XDB-C₁₈ column (4.6 mm×50 mm,3.5 μm) was used for the determination of analyte. And mobile phase was consisted of[0.1% formic water (A)] and[acetonitrile containing 0.1% formic acid (B)] for gradient elution,the flow rate was 0. 45 mL/min. The analytes were detected by multiple reaction monitoring (MRM) mode by negative ion mode in multiple reaction monitoring with electrospray ionization (ESI).[Results] The methodological results met the requirements. The pharmacokinetic parameter T_max was 10~40 min,and t_1/2 was 3.34~8.38 h. C_max and AUC_0-∞ were in the order of salvianolic acid B > danshensu > lithospermic acid > rosmarinic acid > protocatechuic aldehyde > salvianolic acid A.[Conclusion] The method was proved to be specific and repeatable,and to be suitable for determination of phenolic acids in rat plasma for pharmacokinetic study.