HPLC/MS法测定人血浆中氯雷他定的浓度及人体生物等效性

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

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17I服氯雷他定20mg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，pmax为（16．41±2．83）μg·L^-1，t1／2为（9．56±4．21）h，用梯形法计算，AuCo-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，Pmax为（16．45±2．42）μg·L^-1，t1／2为（8．89±4．06）h，用梯形法计算，AuCo-t。为（43．67±9．55）μg·h·L^-1，以AuCo-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。

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 0.5-20.0μg· L- 1. The limit of quantity was 0.5 μg· L- 1. Pharmacokinetic parameters of loratadine reference formulation was obtained as fol- lows： t max was （0.94±0.21 ） h, pmax was （16.41±2.83） μg· L- 1, t 1/2 was （9.56±4.21 ） h, AUC0_t was （38.70 ±6.93）μg·h· L- 1, pharmacokinetic parameters of loratadine test formulation was obtained as fol- Iows：tmax was （0.94±0.21） h, pmax was （16.45±2.42） μg·L-l, t1/2 was （8.89±4.06） h, AUC0.t was （43.67 ± 9.55） μg· h· L- 1. Calculated with AUCo-t, the bioavailability of two formulations was （113.4 ±19.0） %. Conclusions The method is proved to he suitable for bioequivalence evaluation of loratadine.