目的 研究复方麝香黄芪滴丸中7个活性成分（Z-藁本内酯、芒柄花素、毛蕊异黄酮、刺芒柄花苷、毛蕊异黄酮葡萄糖苷、苦杏仁苷、芍药苷）在正常大鼠与脑缺血再灌注损伤模型大鼠的药动学过程，探讨其药动学规律差异。方法 SD大鼠ig复方麝香黄芪滴丸后采集不同时间点血浆，应用超高效液相色谱⁃四极杆/静电场轨道阱高分辨质谱（UHPLC-Q-Orbitrap HRMS）测定血药浓度，采用Kinetica 5.1药动学软件计算各给药组中7个成分的药动学参数，并使用SPSS单因素方差分析药动学参数在ig低、中、高剂量复方麝香黄芪滴丸的正常大鼠和脑缺血再灌注损伤模型大鼠体内是否存在显著性差异。结果 7个生物活性成分的某些药动学参数在正常大鼠和脑缺血再灌注损伤模型大鼠体内有显著性差异。各剂量下的Z-藁本内酯的达峰浓度（C_max）均较正常组明显升高，药时曲线下面积（AUC）在低剂量时明显增加；毛蕊异黄酮、毛蕊异黄酮葡萄糖苷、苦杏仁苷和芍药苷AUC有所降低；毛蕊异黄酮、毛蕊异黄酮葡萄糖苷的半衰期有所增加。结论 为进一步探讨复方麝香黄芪滴丸治疗脑缺血疾病的作用机制奠定基础，为临床制定科学合理的用药策略提供参考。

Objective To study the effects of seven active components (Z-ligustilide, formononetin, verbasin, formononetin, verbasin glucoside, amygdalin, and paeoniflorin) in Compound Shexiang Huangqi Dropping Pills (复方麝香黄芪滴丸) in normal rats and rats with cerebral-ischemia reperfusion injury, and explore its difference in the pharmacokinetics. Methods The plasma of SD rats was collected at different time points after ig Compound Shexiang Huangqi Dropping Pills, plasma concentrations were determined by ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Kinetica 5.1 pharmacokinetic software was used to calculate the pharmacokinetic parameters of seven components in each administration group, and SPSS One-way ANOVA was used to analyze whether there was a significant difference of pharmacokinetic parameters in normal rats and rats with cerebral ischemia-reperfusion injury after ig low-, medium-and high-dose Compound Shexiang Huangqi Dropping Pills. Results Some pharmacokinetic parameters of seven bioactive components were significantly different between normal rats and rats with cerebral ischemia-reperfusion injury. Compared with normal group, peak concentration (C_max) of Z-ligustilide at each dose was significantly increased, area under the curve (AUC) was significantly increased at low-dose; AUC of mullein, mullein glucoside, amygdalin and paeoniflorin were decreased; Half-life of mullein and mullein glucoside were increased. Conclusion It lays a foundation for further exploring the mechanism of Compound Shexiang Huangqi Dropping Pills in the treatment of cerebral ischemia, and provides a reference for formulating scientific and rational drug use strategies in clinical practice.

R285.61

国家自然科学基金资助项目(81974564);中原英才计划-科技创新领军人才项目(224200510027);河南省高等学校重点科研项目(20B360003);河南中医药大学校级科研项目(2019KYCX019)