[关键词]
[摘要]
目的 探究紫辛鼻鼽颗粒主要入血成分木兰花碱、水合氧化前胡素、木兰脂素、五味子醇甲在大鼠体内的药动学特征。方法 采用UPLC-MS/MS技术,测定SD大鼠单次ig给予紫辛鼻鼽颗粒2.52、5.04、10.08 g·kg-1,以及多次ig给予5.04 g·kg-1后,上述4个成分在不同时间点的血药浓度;利用DAS3.2.8软件计算药动学参数,分析其药动学行为。结果 建立的UPLC-MS/MS分析方法可同时测定大鼠血浆中4种指标成分,该方法专属性、准确度、精密度、提取回收率、基质效应和稳定性结果均符合生物样本定量分析要求。大鼠单次给药后,水合氧化前胡素、木兰脂素和五味子醇甲的药时曲线下面积(AUC0~t)与给药剂量呈良好的线性关系(R2>0.9);与单次给药相比,多次给药后4个成分的药动学行为基本一致,AUC0~t和半衰期(t1/2)均无显著性差异。结论 大鼠单次ig紫辛鼻鼽颗粒后,水合氧化前胡素、木兰脂素和五味子醇甲在体内呈线性动力学特征,木兰花碱则表现为非线性动力学过程;多次给药后各成分在体内无蓄积现象。
[Key word]
[Abstract]
Objective To investigate the pharmacokinetic characteristics of the main blood components of Zixin Biqiu Granules, namely magnoflorine, hydrated oxypeucedanin, magnolin, and schisandrin, in rats. Methods UPLC-MS/MS technology was used to determine the blood concentrations of the four components at different time points after single oral administration of 2.52, 5.04, and 10.08 g·kg-1 and multiple oral administration of 5.04 g·kg-1 of the granules to SD rats. The pharmacokinetic parameters were calculated using DAS3.2.8 software, and their pharmacokinetic behaviors were analyzed. Results The established UPLC-MS/MS analytical method could simultaneously determine the four indicator components in plasma. The specificity, accuracy, precision, extraction recovery, matrix effect, and stability results of the method all met the requirements for quantitative analysis of biological samples. After single administration to rats, the area under the plasma concentration-time curve (AUC0~t) of hydrated oxypeucedanin, magnolin, and schisandrin showed a good linear relationship with the dose (R2 > 0.9). Compared with single administration, the pharmacokinetic behaviors of the four components after multiple administrations were basically the same, and there were no significant differences in AUC0~t and half-life (t1/2). Conclusion After single oral administration of Zixing Biqiu Granules to rats, hydrated oxypeucedanin, magnolin, and schisandrin showed linear pharmacokinetic characteristics in vivo, while magnoflorine exhibited nonlinear pharmacokinetic processes. There was no accumulation of the components in vivo after multiple administrations.
[中图分类号]
R969.1
[基金项目]
国家工信部重点创新中药/新型天然药物项目(2440STCZB2614)