HPLC-MS/MS测定人血浆阿奇霉素浓度及生物等效性研究

Study on Determination of Azithromycin in Human Plasma by HPLC-MS/MS and Its Bioequivalent

关键词:  阿奇霉素颗粒  药动学  生物等效性  HPLC-MS/MS

Key words:  azithromycin granules  pharmacokinetic  bioequivalent  HPLC-MS/MS

摘要:

目的 建立人血浆中阿奇霉素的高效液相色谱/质谱/质谱(HPLC-MS/MS)测定法，测定受试者口服阿奇霉素颗粒后的血药浓度，并对受试制剂与参比制剂的生物等效性进行评价。方法 19名健康受试者采用随机双交叉试验设计，单剂量口服阿奇霉素颗粒受试制剂和参比药物各500 mg，用HPLC-MS/MS测定用药后不同时间血药浓度。血药浓度-时间数据经DAS 2.0统计软件处理，计算主要药动学参数，并进行两种制剂的生物等效性评价。结果 受试制剂和参比制剂的T_max分别为(2.5±1.1)h和(2.6±1.7)h，C_max分别为(574.6±209.2) ng·mL^-1和(594.5±229.9) ng·mL^-1，t_1/2分别为(44.7±15.2) h和(42.0±13.0) h，AUC_0-144分别为(5 319.6±2 507.8) h·ng·mL^-1和(5 710.7±2 710.1)h·ng·mL^-1，AUC^_0-∞分别为(5 704.2±2 858.7) h·ng·mL^-1和(6 010.0±2 808.1) h·ng·mL^-1, 以AUC_0-144计算，相对生物利用度为(94.2±15.7)%。两制剂的主要药动学参数无显著性差异。结论 受试制剂与参比药物生物等效。

Abstract:

OBJECTIVE To develop an HPLC-MS/MS assay for determination of azithromycin in human plasma and to investigate the pharmacokinetics and bioequivalence of azithromycin granules in healthy volunteers. METHODS Ninteen volunteers were randomly divided into two groups (test and reference), with double cross over design, a single oral dose of 500 mg of test and reference azithromycin granules was administered to each volunteer. The concentration of azithromycin in plasma was determined by HPLC-MS/MS and pharmacokinetic parameters were calculated by DAS 2.0 practical pharmacokinetics program. RESULTS The main pharmacokinetic parameterswere of test and reference azithromycin granules were as follows: t1/2 were (44.7 ±15.2) h and(42.0 ±13.0) h; T_max were (2.5 ±1.1) h and (2.6 ±1.7) h; C_max were (574.6±209.2) ng·mL^-1 and (594.5 ±229.9)ng·mL^-1 ; AUC_0-144 were(5 319.6±2 507.8) h·ng·mL^-1 and (5 710.7±2 710.1) h·ng·mL^-1; AUC_0-∞ were(5 704.2±2 858.7) h·ng·mL^-1 and(6 010.0±2 808.1) h·ng·mL^-1. The relative bioavailability of tested to reference granules was (94.2±15.7)% according to AUC_0-144. CONCLUSION The two formulations were bioequivalent.