基于UPLC-MS/MS法测定克拉霉素血药浓度的生物等效性研究  

Quantification of clarithromycin in human plasma using UPLC MS/MS for bioequivalence study

作　　者：谭亲友[1,2] 张俊[1,2] 李焕德[1] 朱荣华[1] 彭文兴[1] 

机构地区：[1]中南大学湘雅二医院临床药学教研室,长沙410011 [2]中南大学药学院,长沙410013

出　　处：《药物分析杂志》2010年第7期1282-1286,共5页Chinese Journal of Pharmaceutical Analysis

摘　　要：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tmax为(1.49±0.81)h,Cmax为(2416.8±576.2)ng.mL-1,AUC0→24为(15547.7±4001.5)ng.h.mL-1,AUC0?为(16243.3±4375.0)ng.h.mL-1,t1/2为(5.06±1.39)h;受试制剂的主要药动学参数tmax为(1.72±0.86)h,Cmax为(2125.8±765.7)ng.mL-1,AUC0→24为(15366.4±4167.1)ng.h.mL-1,AUC0?为(16654.9±4361.3)ng.h.mL-1,t1/2为(6.52±2.92)h。受试制剂的相对生物利用度F0→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： tmax were（1.49±0.81）h,Cmax were（2416.8±576.2） ng·mL^-1,AUC0→24 were（15547.7±4001.5） ng·h·mL^-1,AUC0→∞ were（16243.3±4375.0） ng·h·mL^-1 t1/2 were（5.06±1.39）h;The pharmacokinetic parameters of test formulation were as followings： tmax were（1.72±0.86）h,Cmax were（2125.8±765.7）ng·mL^-1,AUC0→24 were（15366.4±4167.1）ng·h mL^-1,AUC0→∞ were（16654.9±4361.3）ng h m·mL^-1 t1/2 were（6.52±2.92）h.The relative bioavailability of clarithromycin based on the AUC0→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.

关 键 词：克拉霉素 UPLC-MS/MS 血药浓度 药动学 生物等效性 

分 类 号：R917[医药卫生—药物分析学]