RP-HPLC测定西洛他唑的血药浓度及药动学研究

 目的建立RP-HPLC测定人血浆中西洛他唑含量,并研究西洛他唑片在健康人体内的药动学。方法色谱柱为HypersilODS-2(4.6 mm×150 mm,5μm)柱,流动相为乙腈-水(45∶55),流速1.0 mL·min^-1,柱温35℃,检测波长254 nm。结果西洛他唑在25～2 000μg·L^-1内线性关系良好(r=0.999 2),血浆最低检测浓度为10μg·L^-1,日内及日间RSD均小于6%,在3种不同浓度下,平均回收率分别为102.71%,102.03%和99.01%。人体药动学研究表明,药-时曲线符合二房室模型,主要药动学参数t_max 3.7 h,ρ_max749.2μg·L^-1,AUC_0～48 10 088.5μg·h·L^-1,t_1/2α 2.5 h,t_1/2β11.9 h。结论此法简便、灵敏、准确、稳定,可用于药物分析,其药动学参数可为临床合理用药提供理论依据。

Determination of Cilostazol in Human Plasma by RP-HPLC:Application to Its Pharmacokinetics

OBJECTIVE To establish a reversed phase HPLC method for the determination of cilostazol in human plasma and to study its pharmacokinetics in healthy volunteers.METHODS A hypersil ODS-2 column(4.6 mm×150 mm,5 μm)was used.The mobile phase consisted of acetonitrile-water(45∶55) with a flow rate of 1.0 mL·min^-1,and the ultraviolet wavelength was at 254 nm.RESULTS The calibration curve was linear over the range of 25～2 000 μg·L^-1(r=0.999 2)and the quantitative limit was 10 μg·L^-1.The intra-and inter-assay coefficient of variation were less than 6% at all levels.The average recoveries were 102.71%,102.03% and 99.01%,respectively.The plasma concentration-time course followed a 2-compartment open model and its main pharmacokinetic parameters were as follows: t_max 3.7 h,ρ_max 749.2 μg·L^-1,AUC_0～48 10 088.5 μg·h·L^-1,t_1/2α 2.5 h,t_1/2β 11.9 h.CONCLUSION This method is easy,sensitive,accurate and stable and is suitable for the pharamacokinetic study of cilostazol.