高效液相色谱法测定人血浆中奥沙普秦的浓度及其生物等效性评价

Determination of oxaprozin in human plasma by HPLC and its bioavailability

目的建立人血浆中奥沙普秦浓度的HPLC测定方法,并评价奥沙普秦的药动学特征及2种奥沙普秦的生物等效性。方法22名男性健康受试者分别单剂量交叉口服受试和参比制剂各0.4 g,采用HPLC法测定人血浆中奥沙普秦的药物浓度,利用Winnonlin 7.0计算药代动力学参数,并计算生物利用度。结果人血浆中奥沙普秦在0.5015~80.24μg·mL^-1与峰面积线性关系良好,最低定量限可达0.5μg·mL^-1;奥沙普秦平均提取回收率大于87.0%;高、中、低3种浓度的批内和批间精密度的RSD值均小于15.0%;受试制剂与参比制剂的主要药代动力学参数如下:t1/2分别为(55.76±10.14)和(50.85±12.34)h,tmax分别为(7.773±9.35)和(6.091±2.599)h,Cmax分别为(59.24±12.07)和(56.05±11.85)μg·mL^-1;AUC0~264 h分别为(3099±1393)和(3228±1078)h·μg·mL^-1;受试制剂的相对生物利用度F0~264 h、F0~∞分别为(95.49±17.46)%、(96.12±18.10)%。结论该方法专属性强、简便、准确,适合于奥沙普秦血药浓度的测定。两种奥沙普秦肠溶胶囊生物等效。

Objective To determine oxaprozin in human plasma by HPLC,and to evaluate the pharmacokinetics and bioequivalence of two oxaprozin capsules in healthy volunteers.Methods Totally 22 healthy male volunteers were given a single oral dose of the test and reference preparation 0.4 g by crossover design,respectively.The concentrations of oxaprozin in the plasma were detected by HPLC,the pharmacokinetic parameters and the bioavailability were calculated by Winnonlin 7.0.Results The oxaprozin in the plasma showed good linearity at 0.5015-80.24μg·m L^-1 and the lower limit of quantification was 0.5μg·mL^-1.The average extraction recovery of oxaprozin was higher than 87.0%.The RSD values of intra-and interassay precision of high,medium and low concentrations were all less than 15.0%;The main pharmacokinetic parameters of the test and reference preparation were as follows:t1/2(55.76±10.14)and(50.85±12.34)h;tmax(7.773±9.35)and(6.091±2.599)h;Cmax(59.24±12.07)and(56.05±11.85)μg·mL^-1;AUC0~264 h(3099±1393)and(3228±1078)h·μg·mL^-1.F0~264 h and F0~∞were(95.49±17.46)%and(96.12±18.10)%.Conclusion The method is specific,simple and accurate and suitable for determine the drug plasma concentration of oxaprozin.The two preparations are bioequivalent.