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

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

目的 :建立反相高效液相色谱法测定血浆中依帕司他浓度 ,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 μBondapakC18(30 0mm× 3.9mm ,1 0 μm)柱 ,流动相 :甲醇 0 .0 1mol·L-1K3 PO4 乙腈 (5 0∶37∶1 3) ,流速 1 .4ml·min-1,设程序波长 0～ 4min 389nm ,4～ 7min 2 37nmUV检测。结果 :该方法回收率为1 0 1 .0 9%～ 1 0 5 .97% ,最低检测浓度为 5 .1ng·ml-1,日内RSD <4.48% (n =5 ) ,日间RSD <4.5 3% (n =5 ) ,线性范围 :2 0 .4～ 1 2 75 0ng·ml-1。 1 0例健康青年志愿者单剂量 po依帕司他片剂 5 0mg后 ,达峰时tmax为 (1 .79± 0 .5 7)h ,峰血药浓度cmax为(3840 .6± 96 8.5 )ng·ml-1,消除半衰期t1/2 β为 (1 .1 1± 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。

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 -1 and 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.