橄榄苦苷在大鼠体内药代动力学研究

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0.113 μg/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.

Pharmacokinetics of Oleuropein in Rats

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(α)was 2.164h,t1/2(β) was 35.292 h,Cmax was 0.113μg/μl,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.