用LC-MS测定人血浆中氯雷他定的浓度及其药动学研究(英文)

Quantitative determination of loratadine in human plasma using liquid chromatography-electron ionization mass spectrometry and studies on its pharmacokinetics

目的 本文建立了专属、灵敏的液质联用方法,用于人血浆中氯雷他定浓度的测定。方法 血样采用乙酸乙酯提取分离后,用质谱检测器的选择性离子检测模式(SIM)测定。结果 该方法的线性范围为0 .1～2 0mg·L-1(r =0 .9994 ) ,方法回收率在96 .8%～10 7.2 %之间,日内和日间RSD <13%。参比制剂和受试制剂的主要药动学参数cmax分别为(4.6 0±2 .4 3)和(4.85±2 .30 )mg·L-1,AUC0→2 4为(19.5 6±10 .2 4 )和(19.2 8±9.4 3)mg·h·L-1,T1/ 2 为(3.5 7±1.5 )和(3.15±1.2 )h ;tmax为(1.2±0 .4 )和(1.3±0 .5 )h。统计学结果表明:2种制剂间的主要动力学参数无明显差异,为生物等效制剂,其相对生物利用度为(98.6±7.2 ) %。结论 该法专属、灵敏,适用于氯雷他定药动学研究。经统计学分析。

AIM To develop a sensitive and specific method for the determination of loratadine in human plasma by LC-MS. METHODS Loratadine was extracted from human plasma by ethyl acetate and analyzed by LC-MS. Selected ion monitoring(SIM)was used to detect loratadine and its internal standard. RESULTS The calibration curve of loratadine was linear within the range of 0.1-20 mg·L -1,with r= 0.9994. The recovery of this method was within 96.8%-107.2%,within day and between day RSD were less than 13%.The pharmacokinetic parameters of the reference and test formulations were(4.60±2.43)and(4.85±2.30)mg·L -1 for c max;(19.56±10.24) and (19.28±9.43) mg·h·L -1 for AUC 0→24;(3.57±1.5) and (3.15±1.2)h for T 1/2;(1.2±0.4) and (1.3±0.5)h for t max respectively.Results from statistic analysis showed that there were no significant differences between the c max,AUC 0→24,T 1/2 and t max values of the two formulations. The relative bioavailability of tablet I with respect to tablet Ⅱ was (98.6±7.2)% from the AUC 0→24 measurement. Bioequivalance was observed between the two tablets. CONCLUSION The method is specific and sensitive,it is suitable for the pharmacokinetic research of loratadine in human plasma.The results demonstrate that the two preparations are bioequivalent.