依帕司他血药浓度测定方法及其在药代动力学研究中的应用

 目的：建立反相高效液相色谱法测定血装中依帕司他浓度，研究该药物在人体内的药代动力学。方法：血浆样品用甲醇沉淀蛋白后直接进样，选地西泮作内标。采用μBpndapak C〈sub〉18〈/sub〉（300 mm×3.9 mm，10 μm）柱，流动相：甲醇-0.O1 mol·L〈sup〉-1〈/sup>K〈sub〉3〈/sub〉PO〈sub〉4〈/sub〉-乙腈(50：37：13)，流速1.4 ml·min〈sup〉-1〈/sup>，设程序波长0～4 min 389 nm，4～7 min 237 nm UV检测。结果：该方法回收率为101.09%～105.97%，最低检测浓度为5.1ng·ml〈sup〉-1〈/sup>，日内RSD<4.48%(n=5)，日间RSD<4.53%(n=5)，线性范围：20.4～12750 ng·ml〈sup〉-1〈/sup>。10例健康青年志愿者单剂量po，依帕司他片剂50 mg后，达峰时t〈sub〉max〈/sub〉为(1.79士0.57)h，峰血药浓度c〈sub〉max〈/sub〉为(3840.6±968.5)ng·ml〈sup〉-1〈/sup>，消除半衰期t〈sub〉1/2β〈/sub〉为((1.11±0.35)h。结论：本法快速，准确，灵敏，能较好地满足依帕司他临床药代动力学研究需要。

Determination of epalrestat in human plasma by high performance liquid chromatography and its pharmacokinetics

OBJECTIVE:To develop a reversed phase liquid chromatographic method for the determination of epalrestat in human plasma and study its pharmacokinetics.METHODS:The plasma sample was injected directly for determination after being deproteinized with methanol and the 3P87 pharmacokinetic software was used for the calculation of pharmacokinetic parameters.RESULTS:The linear range was 20.4～12750 ng·ml^-1,the limitation of detection was 5.1 ng·ml^-1,within day RSD＜4.48%(n=5),between day RSD＜4.53%(n=5),the recoveries of epalrestat were 101.09%～105.97%.After oral administration of 50 mg of epalrestat tablet,the results showed that the disposition of epalrestat was conformed to a two compartment model with t_1/2α=(0.56±0.24) h,t_1/2β=(1.11±0.35) h,t_max=(1.79±0.57) h,c_max=(3840.6±968.5) ng·ml^-1and AUC_0～∞=(13016±2865.4) ng·h·ml^-1.CONCLUSION:This method is rapid,accurate and sensitive,it is very suitable for the investigation of clinical pharmacokinetics of epalrestat.