橄榄苦苷在大鼠体内药代动力学研究

Pharmacokinetics of Oleuropein in Rats

目的建立测定大鼠血浆中橄榄苦苷浓度的HPLC方法,研究橄榄苦苷在大鼠体内的药代动力学过程。方法雄性Wistar大鼠,灌胃给予橄榄苦苷100 mg·kg-1,于不同时间点收集血液。以甲醇-水-甲酸(63∶37∶1)为流动相,Agi-lent C18为色谱柱,在紫外波长276 nm下检测,应用药代动力学软件3p97拟合房室模型,并进行药代动力学参数的计算。结果选定条件下橄榄苦苷峰形良好,线性范围为0.052～0.263 mg/ml,日内日间精密度RSD均小于3%,准确度RE为-0.190%,加样回收率为96.900%～102.700%。大鼠灌胃橄榄苦苷100 mg·kg-1后,体内药代动力学过程符合二室模型,Tmax为5.440 h,t1/2(α)为2.164 h,t1/2(β)为35.292 h,Cmax为0.113μg/μl,AUC为6.254,CL为15.990。结论该方法灵敏,简便,选择性强,适用于橄榄苦苷血药浓度的测定,及其药代动力学研究。

Objective To establish an HPLC method for the determination of Oleurpein in rat plasma, and to investigate the pharmacokinetic characteristics of oleuropein in healthy rats after a singal oral dose. Methods The blood samples were collected at different time points from male Wistar rats which were administered oleuropein 100 mg . kg-1 and were detected by UV detector at 276nm with a mobile phase consisting of water- methanol- methanoic acid（63： 37： 1 ）and the column Agilent C18. The data obtained were fitted with 3P87 program on computer. Results Under the selected conditions, the peak shape of oleuropein was good, the linear range was 0. 052 - 0. 263mg/ml, day - day precision RSD was less than 3% , accuracy of RE was - 0. 190% , and the recovery rate was 96. 900% - 102. 700%. After the rats were fed oleuropein gentiopicroside 100. 000 mg. kg-1 , the plasma concentration - time curve of oleuropein was fitted with a two - compartment open model with a lag time, Tmax was 5. 440 h, t1/2 （a）was 2. 164h, t1/2 （β） was 35. 292 h , Cmax was 0.113ug/ul, AUC was 6. 254, CL was 15. 990. Conclusion The method is sensitive, simple and selective, and is applicable to the determination of plasma concentrations and pharmacokinetic studies of oleuropein.