HPLC-MS-MS法评价琥乙红霉素颗粒的人体生物等效性

Bioequivalence Study of Erythromycin Ethylsuccinate Granules in Human by HPLC-MS-MS

目的:建立人体血浆中琥乙红霉素的HPLC-MS-MS分析方法,并对受试制剂与参比制剂的生物等效性进行评价。方法:筛选24名健康受试者,随机双周期交叉试验设计,给药剂量为500mg/人,采用LC-MS/MS法测定各受试者服药后不同时间点血浆中活性成分红霉素的血药浓度,计算药代动力学参数,利用DAS软件进行生物等效性评价。结果:受试制剂和参比制剂红霉素的Tmax分别为0.60±0.30h和0.76±0.39h,Cmax分别为778.2±311.4ng/mL和804.7±363.4ng/mL,t1/2分别为2.83±0.84h和3.12±1.26h,AUC0-t分别为2819±1202ng·h/mL和2930±1529ng·h/mL,AUC0-∞分别为3014±1330ng·h/mL和3178±1689ng·h/mL。AUC0-t、AUC0-∞和Cmax的相对生物利用度分别为98.1%、96.7%和97.4%,相应的90%置信区间分别为85.6%～112.3%,84.0%～111.2%和83.6%～113.4%,Tmax无显著性差异。结论:琥乙红霉素颗粒受试制剂与参比制剂具有生物等效性。

Objective： To establish a HPLC - MS - MS method for tile determination of erythromycin ethylsuccinate in human plasma, and to evaluate the bioequivalence of test erythromycin ethylsuccinate granules with reference one. Methods ： A single oral dose of 500 mg erythromycin ethylsuccinate granules of test or reference was given to 24 healthy man volunteers in a two - way cross - over design, a HPLC - MS - MS method was employed to determine drug concentrations in plasma, the pharmaeokinetic parameters were calculated by DAS statistic software to evaluate the Bioequivalenee of human. Results：the main pharmaeokinetic parameters Tmax, Cmax, t1/2, AUC0-t and AUC0-∞ for the test granules were 0. 60 ± 0. 30 h,778. 2 ± 311.4ng/mL,2.83 ±0. 84 h,2819 ± 1202 ng · h/mL and 3014 ± 1330 ng · h/mL,respectively. The main pharmacokinetic parameters Tmax ,Cmax, ,t1/2 ,AUCo-t and AUC0-∞ for the reference granules were 0.76 ± 0. 39 h,804. 7 ±363.4 ng/mL,3.12 ±1.26 h,2930 ± 1529 ng·b/mL and 3178±1689 ng·h/mL, respectively. The relative bioavalability of AUC0-t ,AUC0-∞ and Cmax are 98. 1% ,96.7% and 97.4% ,the 90% Confidence interval are 85.6% - 112.3% ,84.0% - 111.2% and 83.6% - 113.4%, respectively, and Tmax have no tipical difference. Conelusion： The test and the reference Erythromycin Ethylsuccinate granules were bioequivalence.