LC-MS法评价2种盐酸非索非那定制剂的人体生物等效性

目的建立LC-MS法测定人血浆中非索非那定浓度,评价盐酸非索非那定胶囊(受试制剂)与盐酸非索非那定片(参比制剂)的人体生物等效性。方法采用Kromasil C18(150 mm×4.6 mm,5μm)色谱柱;流动相:甲醇-质量分数为1%的甲酸水溶液(体积比为88∶12);离子源:大气压化学电离源,扫描方式:选择离子监测,用于定量分析的离子分别为m/z502.15(非索非那定)和m/z383.00(内标氯雷他定)。本法用于健康受试者口服盐酸非索非那定受试制剂和参比制剂的生物等效性研究。结果非索非那定质量浓度在10.0~2000.0μg.L-1内线性关系良好,方法的定量下限(LLOQ)为10.0μg.L-1。受试制剂与参比制剂的主要药物动力学参数:tmax分别为(1.9±0.2)和(1.9±0.2)h;ρmax分别为(173±77)和(183±83)μg.L-1;t1/2分别为(5.6±2.6)和(5.8±2.4)h;AUC0-t分别为(982±583)和(1081±772)μg.h.L-1,AUC0-∞分别为(1 176±738)and(1 271±998)μg.h.L-1。盐酸非索非那定胶囊的相对生物利用度为(90.8±15.3)%(n=18)。结论 2种盐酸非索非那定制剂具有生物等效性。

Bioequivalence study of two kinds of fexofenadine hydrochloride preparations in Chinese healthy volunteers by LC-MS

Objective To establish an LC-MS method for the determination of fexofenadine in human plasma to evaluate the bioequivalence of fexofenadine hydrochloride capsules and tablets.Methods The separation was carried out on a Kromasil C18(150 mm×4.6 mm,5 μm)with a mobile phase of methanol-1%(w)formic acid(V∶V=88∶12).Fexofenadine was determined by LC-APCI/MS in selected ion monitoring(SIM)mode,the ion combination of m/z 502.15 and m/z 383.00 was used to qualify fexofenadine and the internal standard,respectively.Results The calibration curve was in good linearity over the range of 10.0-2 000.0 μg·L-1.The lower limit of quantification(LLOQ)for fexofenadine in plasma was 10.0 μg·L-1.The pharmacokinetic parameters of test capsules and reference tablets were as follows:tmax were(1.9±0.2)and(1.9±0.2)h;ρmax were(173±77)and(183±83)μg·L-1;t1/2 were(5.6±2.6)and(5.8±2.4)h;AUC0-t were(982±583)and(1081±772)μg·h·L-1;AUC0-∞ were(1 176±738)and(1 271±998)μg·h·L-1,respectively.The relative bioavalibility of fexofenadine hydrochloride capsules was(90.8±15.3)%(n=18).Conclusions The statistical analysis shows that the test and reference preparations are bioequivalent.