薏苡仁与花旗泽仁给药后9-HODE在大鼠血浆中的药动学比较

Pharmacokinetics Comparison of 9-HODE after the Administration of HQZR and Yiyiren

目的:通过建立HPLC-MS/MS分析方法,研究单味药薏苡仁及复方花旗泽仁中9-羟基-(10E,12E)-十八碳二烯酸(9-HODE)在大鼠血浆中的比较药代动力学。方法:将雄性SD大鼠随机分为花旗泽仁组和薏苡仁组,分别灌胃给药。于不同时间点进行血浆样品采集,采用HPLC-MS/MS法测定9-HODE的血药浓度。结果:本研究建立的HPLC-MS/MS分析方法,仪器精密度良好,方法专属性较强,各成分的回收率、重现性与稳定性均符合生物样品检测要求,适用于9-HODE的血浆含量检测。9-HODE的主要药动学参数达峰浓度Cmax为802.9±88.64μg/L;达峰时间T_(max)为0.5 h;半衰期t_(1/2)为7.737±3.309 h;药时曲线下面积AUC_(0-t)为1820±154.2μg/L·h;平均滞留时间MRT0-t为5.862±1.304 h;血浆清除率CL为0.190 5±0.013 22 L/h/kg。本实验结果示,与薏苡仁组比较,花旗泽仁组血浆消除率(CL)明显降低(P<0.05),主要药代动力学参数如药时曲线下面积(AUC)、平均滞留时间(MRT)、半衰期(t_(1/2))等未出现显著性差异(P>0.05)。结论:薏苡仁配伍为花旗泽仁后,对9-HODE的血药浓度吸收未产生明显影响,而在消除方面,降低了其在体内的血浆清除率(CL),使9-HODE在体内作用时间延长。

Objective: To compare the pharmacokinetics 9-hydroxy-( 10 E,12 E)-octadecadienoic acid( 9-HODE)from single Yiyiren( YYR) and compound Huaqizeren( HQZR) in the serum of rats by HPLC-MS/MS method.Methods: Male SD rats were randomly divided into HQZR group and YYR group. Plasma concentration of 9-HODE was determined by HPLC-MS/MS method at different time points. Results: The HPLC-MS/MS analysis method established in this study had good precision and method specificity. The recovery,reproducibility and stability of each component were in line with the requirements of biological samples for the detection of plasma 9-HODE. Cmax of 9-HODE was 802. 9 ± 88. 64 μg/L; T_(max) was 0. 5 h; t_(1/2) was 7. 737 ± 3. 309 h,and AUC_(0-t)was 1820 ± 154. 2 μg/L·h;MRT_(0-t)was 5. 862 ± 1. 304 h; CL was 0. 190 5 ± 0. 013 22 L/h/kg. The results of this experiment showed that CL was significantly decreased in HQZR group compared to that in YYR group( P < 0. 05). There were no significant difference between the two groups in terms of AUC,MRT_(0-t),and t_(1/2)( P > 0. 05). Conclusion: HQZR dose not have a significant impact on the blood concentration of 9-HODE absorption,it can reduces CL and prolong the action duration of 9-HODE.