大鼠血浆中利托那韦的HPLC法测定及其药动学研究

Determination of Ritonavir in Rat Plasma by HPLC and Its Pharmacokinetics

目的:建立了测定大鼠血浆中利托那韦的高效液相色谱法,并用于利托那韦在大鼠体内的药动学研究.方法:大鼠血浆样品经乙腈沉淀蛋白后,采用高效液相色谱法测定血浆中利托那韦的含量.选用Agilent Zorbax XDB-C18色谱柱,以乙腈-0.1%磷酸水溶液(55∶45)为流动相,流速1.0mL·min^(-1);柱温35°C,检测波长254nm.结果:该方法下大鼠血浆中利托那韦在0.05-5μg·mL^(-1)浓度范围内线性关系良好;高、中、低浓度下日内和日间RSD值均小于5%;提取回收率在85%^(-1)25%之间;稳定性良好.大鼠灌胃给予利托那韦混悬液(8mg·kg^(-1))后,血浆中利托那韦的药动学参数分别为:Cmax120.30±9.00ng·mL^(-1),Tmax1±0.35h,T1/20.41±0.14h,AUC0-∞624.30±39.88h·(ng·mL^(-1)),AUC0-t789.80±19.73h·(ng·mL^(-1)).结论该方法简单、快速、经济、重复性良好,适用于利托那韦大鼠体内药代动力学的研究.

Objective A HPLC method was established for the determination of ritonavir in rat plasma and its pharmacokinetics in rats was investigated.Method The protein of plasma samples was removed by acetonitrile.An Agilent Zorbax XDB-C18 column was used with the mobile phase of acetonitrile：0.1% phosphoric acid（55∶45）,the flow rate of 1.0 mL·min^（-1） and the column temperature of35℃ at the detection wavelength of 254 nm for the HPLC method.Result The calibration curve was linear in the concentration range of 0.05-5μg·mL^（-1）,with the intra-and inter-day RSDs less than 5%,extraction recoveries of 85%^（-1）25% and excellent stability.After oral administration of 10 mg·kg^（-1） ritonavir suspensions to rats,the main pharmacokinetic parameters were analyzed as follows：Cmax120.30±9.00 ng·mL^（-1）,Tmax1±0.35 h,T1/20.41±0.14 h,AUC0-∞624.30±39.88 h·（ng·mL^（-1））,AUC0-t789.80±19.73 h·（ng·mL^（-1））.Conclusion The method is simple,rapid,economical and reproducible for the determination of ritonavir in rat plasma and is suitable for the pharmacokinetics study in rat.