西洛他唑的高效液相色谱法测定及药动学研究

Determination of cilostazol in human plasma and its pharmacokinetics by HPLC

目的 :建立测定人血浆中西洛他唑含量的高效液相色谱 (HPLC)法 ,并研究西洛他唑片在健康人体内的药动学。方法 :色谱柱为HypersilC18柱(4 .6mm× 2 0 0mm ,5 μm) ,流动相为乙腈 水 (4 5∶5 5 ) ,流速 1.0ml·min-1,柱温 30℃ ,检测波长2 5 4nm ,西洛他唑血浆样品以 2mol·L-1NaOH 无水乙醚 (1∶4 )提取 ,以地西泮为内标。结果 :标准曲线线性范围 2 0～ 2 0 0 0 μg·L-1(r =0 .9999)。血浆中西洛他唑最低检测限为 10 μg·L-1。平均提取回收率为 80 .2 %± 3.6 % ,平均方法回收率为 97.0 %±3.8% ,日内RSD≤ 5 .8% ,日间RSD≤ 10 .1%。应用该法研究了 10例健康志愿者口服 10 0mg西洛他唑后的药动学 ;其体内过程符合二室模型 ,tmax为 3.5 8± 1.0 8h ,Cmax为 92 0± 2 30 μg·L-1,AUC0 -48为 11.0± 3.3mg·h-1·L-1。结论 :此法简便、快速 ,适用于药物分析 ,其药动学数据可为临床合理用药。

AIM: To establish a reversed phase high-performance liquid chromatographic method to determine cilostazol in human plasma and to study the pharmacokinetics of cilostazol in 10 healthy volunteers. METHODS: Using diazepam as the internal standard, cilostazol was extracted from human plasma with a mixture of 2 mol·L -1 NaOH- diethyl ether anhydrous (1:4). The mobile phase was acetonitrile-water (45:55), flow rate 1 ml·min -1, and the UV absorbance wavelength 254 nm. The pharmacokinetic analysis of cilostazol in 10 healthy volunteers after oral administration of 100 mg was studied. RESULTS: Linear range of the standard curve was from 20 to 2 000 μg·L -1 (r= 0.9999). The quantitative limit for cilostazol was 10 μg·L -1. The mean extraction recovery was 80.2%± 3.6%. The mean analytical recovery was 97.0%± 3.8%. The relative standard deviation of intra-day and inter-day did not exceed 5.8% and 10.1%, respectively. It was found to be fitted to a two-compartment open model and its pharmacokinetic parameters were as follow: t max 3.58± 1.08 h, C max 920±230 μg·L -1 AUC 0-48 11.0± 3.3 mg·h -1·L -1, respectively. CONCLUSION: The method is suitable for drug monitoring of cilostazol and the pharmacokinetics of cilostazol in human provides a useful index for clinical trial.