HPLC/MS法测定人血浆中氯雷他定的浓度及人体生物等效性

目的建立测定人血浆中氯雷他定的LC/MS方法,并应用于药物制剂生物等效性研究。方法18名健康受试者单剂量口服氯雷他定20 mg后,血浆样品经液液萃取,通过液相色谱质谱联用法测定其质量浓度,并计算药动学参数。结果氯雷他定测定方法的线性为0.5~20.0μg.L-1,定量下限为0.5μg.L-1;参比制剂的主要药动学参数tmax为(0.94±0.21)h,ρmax为(16.41±2.83)μg.L-1,t1/2为(9.56±4.21)h,用梯形法计算,AUC0~t为(38.70±6.93)μg.h.L-1;受试制剂的主要药动学参数tmax为(0.94±0.21)h,ρmax为(16.45±2.42)μg.L-1,t1/2为(8.89±4.06)h,用梯形法计算,AUC0~t为(43.67±9.55)μg.h.L-1,以AUC0-t计算,受试制剂相对生物利用度为(113.4±19.0)%。结论该法适用于氯雷他定制剂的生物等效性评价。

Determination of loratadine in human plasma and its bioequivalence by HPLC/MS method

Objective To develop a sensitive and specific LC/MS method for direct determination of loratadine in human plasma and study the bioequivalence of different formulations containing loratadine.Methods After a single dose oral administration of loratadine 20 mg to 18 healthy Chinese male volunteers,the plasma concentrations of loratadine were determined.Loratadine and internal standard diazepam were extracted from plasma using liquid-liquid extraction.Plasma concentration of loratadine was determined by HPLC-MS,and the pharmacokinetic parameters of loratadine in different formulations were calculated.Results The linear calibration curves were obtained in the concentration range of 0.5～20.0 μg·L~(-1).The limit of quantity was 0.5 μg·L~(-1).Pharmacokinetic parameters of loratadine reference formulation was obtained as follows:t_(max) was(0.94±0.21) h,ρ_(max) was(16.41±2.83) μg·L~(-1),t_(1/2) was(9.56±4.21) h,AUC_(0-t) was(38.70±6.93) μg·h·L~(-1),pharmacokinetic parameters of loratadine test formulation was obtained as follows:t_(max) was(0.94±0.21) h,ρ_(max) was(16.45±2.42) μg·L~(-1),t_(1/2) was(8.89±4.06) h,AUC_(0t) was(43.67±9.55) μg·h·L~(-1).Calculated with AUC_(0-t),the bioavailability of two formulations was(113.4±19.0)%.Conclusions The method is proved to be suitable for bioequivalence evaluation of loratadine.