论文部分内容阅读
目的:建立人血浆中非索非那定的LC-MS/MS测定方法,并研究其在健康人体内的药动学特征。方法:以格列吡嗪为内标,血样经甲醇沉淀法提取,采用Agilent ZORBAX SB-C_(18)(100 mm×2.1 mm,3.5μm),以甲醇-10 mmol·L~(-1)醋酸铵水溶液(70:30)为流动相,流速0.20 ml·min~(-1);质谱选择性检测非索非那定和内标格列吡嗪离子对分别为m/z 502.1→466.2,446.0→321.1。20名健康受试者分成两组,分别进行低、中单剂量和多剂量给药的药物动力学试验。结果:非索非那定的线性范围为1.0～600.0 ng·ml~(-1)(r=0.997 6,n=5),定量下限为1.0 ng·ml~(-1),提取回收率>87.6%,日内和日间RSD≤8.5%。非索非那定的t_(1/2)为(9.29～11.14)h,MRT为(7.95～8.24)h;多剂量给药后C_(ss,max)为(206.89±123.23)ng·ml~(-1),AUC_(ss)为(1122.98±646.60)ng·h·ml~(-1),DF为(1.81±0.36)。结论:该法灵敏、简便、快捷、准确、重现性好,适用于非索非那定血药浓度测定及人体药动学研究。
Objective: To establish a LC-MS / MS method for the determination of fexofenadine in human plasma and study its pharmacokinetics in healthy volunteers. METHODS: Glipizide was used as an internal standard and the blood samples were extracted by methanol precipitation. The samples were separated by methanol (10 mmol·L -1) with Agilent ZORBAX SB-C 18 (100 mm × 2.1 mm, 3.5 μm) Ammonium acetate aqueous solution (70:30) was used as the mobile phase at a flow rate of 0.20 ml · min -1. The ion pair pairs for fexofenadine and internal standard glipizide were m / z 502.1 → 466.2, 446.0 → 321.1.20 Healthy subjects were divided into two groups and their pharmacokinetic tests were performed on low, medium, and multiple doses, respectively. Results: The linear range of fexofenadine was 1.0-600.0 ng · ml -1 (r = 0.997 6, n = 5), and the lower limit of quantitation was 1.0 ng · ml -1. The extraction recovery was> 87.6%, day and day RSD ≤ 8.5%. The mean t_ (1/2) of fexofenadine was (9.29 ~ 11.14) h and the MRT was (7.95 ~ 8.24) h. The C_ (ss, max) after the multidose administration was (206.89 ± 123.23) ng · ml ~ (-1), AUC (ss) was (1122.98 ± 646.60) ng · h · ml -1, DF was (1.81 ± 0.36). Conclusion: The method is sensitive, simple, rapid, accurate and reproducible. It is suitable for the determination of fexofenadine and its pharmacokinetics.