高效液相色谱法测定瑞巴匹特的血药浓度及其药代动力学研究

HPLC assay for determination of rebamipide in plasma and its pharmacokinetic investigation

目的：建立血浆中瑞巴匹特浓度的高效液相色谱分析方法，并用此方法研究瑞巴匹特在人体内的药代动力学。方法：血样经酸化，用乙酸乙酯单步萃取后，以甲醇ｐＨ３的磷酸盐缓冲液（５２∶４８）为流动相，在紫外２３０ｎｍ处检测。所得数据用３ｐ８７药代动力学程序处理，求出相应的参数。结果：瑞巴匹特血浓度在２０～１２００μｇ·Ｌ－１范围内与色谱峰高呈良好线性关系，血浆中药物最低检测浓度为１０μｇ·Ｌ－１，日内及日间ＲＳＤ（ｎ＝５）分别在１．１１％～３．７２％和３．８７％～７．６０％，方法回收率为９９．８４％～１００．２０％。药代动力学研究表明，口服国产和进口瑞巴匹特片剂的血药浓度时间曲线均符合一级吸收一级消除的一房室模型，体内药物达峰时间分别为（１．９５±０．７３）ｈ和（１．５７±０．５５）ｈ；ｃｍａｘ分别为（５１０．８±１５２．０）μｇ·Ｌ－１和（５６４．８±１８７．７）μｇ·Ｌ－１；ｔ１／２分别为（１．７５±０．６３）ｈ和（１．６６±０．３）ｈ；国产瑞巴匹特片的相对生物利用度为（９９．３６±７．８７）％。结论：此方法简便、可靠，测定灵敏度高，能较好地满足瑞巴匹特临床血药浓度监测及人体内药代动力学的研究。

OBJECTIVE: To establish a HPLC method for the determination of rebamipide in human plasma and investigate the pharmacokinetic characteristics of rebamipide in healthy volunteers after a singal oral dose.METHODS: The drug was extracted from plasma with ethyl acetate after acid purification,and then detected by UV detector at 230nm with a mobile phase consisting of methanol:phosphate buffer (5248).The data obtained were fitted with 3P87 program on computer. RESULT: A linear relationship was obtained between the peak height and the concentration of rebamipide from 20gL-1 to 1200gL-1 and the limit of detection was 10gL-1.The average relative deviations (RSD) of within day and between day variation were 1.113.72% and 3.877.60% (n=5) respectively.The recoveries of rebamipide were 99.48100.20%.The results showed that the plasma concentrationtime curve of the two preparations were all fitted to a onecompartment model with first order absorption and elimination.Tpeak of domestic and imported tablets were 1.95 0.73 and 1.570.55h;cmax were 510.8152.0 and 564.8187.7gL-1;t1/2 were 1.750.63 and 1.660.31h;respectively.WT5HZCONCLUSION: This experiment established a simple,highly sensitive and selective method for the determination of plasma rebamipide levels in humans.It provides a suitable analysis method for its pharmacokinetic studies.