基于UPLC-MS/MS法测定克拉霉素血药浓度的生物等效性研究

目的: 建立人血浆中克拉霉素的超高效液相色谱串联质谱(UPLC-MS/MS)的测定方法;研究克拉霉素胶囊在健康人体中的药动学和生物等效性。方法:采用随机、开放、双周期交叉试验设计,18名健康受试者分别口服受试制剂和参比制剂500 mg。采用UPLC-MS/MS法测定给药后各时间点采集血样中克拉霉素血药浓度,计算主要药物动力学参数,评价其生物等效性。结果:参比制剂的主要药动学参数t_max为(1.49±0.81)h,C_max为(2416.8±576.2)ng·mL^-1,AUC_0→24为(15547.7±4001.5)ng·h·mL^-1,AUC₀ SymbolnB@ SymboleB@ 为(16243.3±4375.0)ng·h·mL^-1 ,t_1/2 为(5.06±1.39)h;受试制剂的主要药动学参数t_max为(1.72±0.86)h,C_max为(2125.8±765.7)ng·mL^-1,AUC_0→24为(15366.4±4167.1)ng·h·mL^-1,AUC₀ SymbolnB@ SymboleB@ 为(16654.9±4361.3)ng·h·mL^-1,t_1/2为(6.52±2.92)h。受试制剂的相对生物利用度F_0→24为102.9%±16.6%。结论:本方法准确、灵敏、简便。统计学结果表明,2种制剂具有生物等效性。

Objective: To develop an ultra performance LC-tandem mass spectrometry (UPLC-MS/MS) method to study the pharmacokinetics and bioequivalence of clarithromycin in healthy volunteer. Method: According to a randomized cross-over design, A single oral dose of 500 mg clarithromyci (test or compare preparations) was given to 18 healthy volunteers, The concentration of clarithromyci in plasma was detected by UPLC-MS/MS, The main pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations. Results: The pharmacokinetic parameters of reference formulation were as followings: t_max were(1.49±0.81)h, C_max were(2416.8±576.2) ng·mL^-1, AUC_0→24 were(15547.7±4001.5) ng·h·mL^-1, AUC₀ SymbolnB@ SymboleB@ were (16243.3±4375.0) ng·h·mL^-1 t_1/2 were(5.06±1.39)h; The pharmacokinetic parameters of test formulation were as followings: t_max were(1.72±0.86)h, C_max were(2125.8±765.7)ng·mL^-1, AUC_0→24 were(15366.4±4167.1)ng·h mL^-1, AUC₀ were (16654.9±4361.3)ng h m·mL^-1 t_1/2 were(6.52±2.92)h. The relative bioavailability of clarithromycin based on the AUC_0→24 data was 102.9%±16.6%.Conclusion:This method is rapid ,highly sensitive and accurate ,and suitable for the pharmacokinetic study of clarithromycin. The two formulation are bioequivalent.