注射用清开灵中栀子苷在家兔体内的药动学研究

Pharmacokinetics of Geniposide in Qingkailing Injection in Rabbits

目的建立高效液相色谱法测定血浆中注射用清开灵主要成分栀子苷的方法 ,研究其在家兔体内的药代动力学,为临床用药提供新的药代动力学参数。方法采用GeminiC18色谱柱(250mm×4.6mm,5μm),流动相:乙腈-水(14∶86),紫外检测波长:238nm,流速:1ml/min,进样量:20μl,柱温:40℃。3只家兔静脉滴注注射用清开灵后,采集不同时间点的血药浓度,计算其药动学参数。结果在选定的色谱条件下,注射用清开灵中栀子苷与血浆中其他成分分离良好。栀子苷的血药浓度范围:0.11～7.32μg/ml(r=0.9979)。栀子苷高、中、低3种浓度方法回收率大于96.3%、萃取回收率大于94.0%;日内和日间精密度RSD分别小于4.9%、3.2%,最低检测限为0.11μg/ml。将血药浓度数据采用3P97软件拟合,结果符合一室模型。栀子苷的主要药动学参数:t1/2为(0.33±0.03)h,V为(0.71±0.10)L,CL为(1.47±0.07)L/h,AUC0→4.5h为(3.71±0.20)μg.h/ml。AUC0→∞(4.22±0.37)μg.h/ml。结论本文方法简便、准确,其药代动力学数据为临床注射用清开灵中栀子苷血药浓度的监测和药代动力学研究提供了依据。

Objective To establish a high performance liquid chromatography method for geniposide in Qingkailing and study pharmacokinetics of geniposide in rabbit plasma in order to provide new pharmakinetic data for clinical use.Methods A high performance liquid chromatography with ultraviolet detection has been developed for determination of geniposide in plasma of rabbits using a Gemini C18 column（250 mm×4.6 mm,5 μm）,with acetonitrile-water as the mobile phase（14∶86）.The flow rate was 1 ml/min with the column temperature at 40℃.The concentration of geniposide for each rabbit was determined at different points of time after intravenous drip for 30 min before their pharmacokinetic parameters were calculated.Results A perfect chromatographic peak of geniposide was observed with excellent separation and reproducibility.The linear range of geniposide in Qingkailing injection was 0.11-7.32 μg/ml（r=0.9979）.The extract recovery of genposide in three different concentrations was respectively more than 96.34% and 94.04%.The RSD of intra-day and inter-day precision was less than 4.9% and 3.2%.The limit of detection was 0.11μg/ml.The drug concentration-time profile conformed to the one-compartment model by 3P97.The t1/2 was（0.33±0.03）h,V was（0.71±0.10）L,CL was（1.47±0.07）L/h,and AUC0→∞ was（4.22±0.37）μg·h/ml.Conclusion This study will provide a simple,sensitive and accurate method for determination of the plasma level of geniposide in Qingkailing and for its pharmacokinetic study.