左金丸微乳凝胶与水凝胶中6种主要生物碱的药代动力学比较研究

Comparative study on pharmacokinetics of six major alkaloids in Zuojin Wan microemulsion based gel and hydrogel

目的:建立HPLC-MS方法同时测定血浆中6种生物碱的浓度以评价2种给药载体中左金丸的主要成分药物动力学过程。方法:家兔经皮给予相同剂量的微乳凝胶和水凝胶后不同时间点采集血浆样本,LC-MS法测定血浆中6种生物碱的浓度,数据以WinNonLin软件拟合,并计算主要药动学参数。结果:以小檗碱、巴马汀、黄连碱、药根碱、吴茱萸碱和吴茱萸次碱为指标成分,与水凝胶比较微乳凝胶的相对生物利用度分别为131%,127%,108%,121%,92%,109%,吸收速率常数之比分别为10.5,5.1,3.7,0.8,1.8,1.5。结论:该方法可同时测定血浆中上述6种生物碱的含量,能快速、简便地进行生物样本分析;药代动力学参数显示,与水凝胶相比,微乳凝胶给药系统能加速药物的经皮吸收速度。

Objective： To compare the pharmcoknetic parameters of six major alkaloids in the two drug delivery system of Zuojin Wan, by LC-MS assaying the six major alkaloids plasma concentration. Method： The blood samples were collected at different time after transdermal administration. The plasma concentration of six major alkaloids were detected by LC-MS, then the concentration^-time data are modulated by software WinNonlin. Result： Took the six alkaloids（berberine palmatine coptisine jateorhizine evodiamine rutecarpine）as index components, the relative bioavailability were 131%, 127%, 108%, 121%, 92%,109%, respectively, the ratio of Ka were 10.5, 5.1, 3.7, 0.8, 1.8,1.5, respectively. Conclusion： The LC-MS can be applied in the determination of six major alkaloids plasma concentration. The pharmcoknetic parameters indicated that Zuojin Wan microemulsion gel delivery system can accelerate the transdermal absorption rate of Zuojin Wan, compared with the hydrogel drug delivery system.