液-质联用测定氯诺昔康国产与进口片剂的人体生物等效性

目的:建立液相色谱-串联质谱法(LC-MS/MS)的检测方法,评价受试与参比的氯诺昔康片在健康人体的生物等效性。方法:采用随机、开放、双周期交叉试验设计,20名中国男性健康受试者单剂量口服受试制剂和参比制剂8 mg后不同时间点的血浆样本经甲醇直接沉淀蛋白,应用LC-MS/MS法测定氯诺昔康的血药浓度,利用DAS 2.0软件计算药动学参数,并进行生物等效性评价。结果:受试制剂和参比制剂的药动学参数如下:Cmax分别为(782.0±275.1)μg·L-1和(823.4±256.1)μg·L-1,tmax分别为(2.8±1.4)h和(2.6±1.4)h,t1/2分别为(3.5±1.2)h和(3.3±0.8)h,AUC0-24 h分别为(4 545±1 714)μg.h.L-1和(4 516±2 054)μg·h.L-1,相对生物利用度为(103.8±15.0)%。结论:建立的分析方法灵敏、简便、准确,统计结果表明受试制剂和参比制剂生物等效。

Bioequivalence study of lornoxicam tablets in healthy volunteers by LC-MS/MS method

OBJECTIVE To develop an LC-MS/MS method for the determination of lornoxicam in human plasma to evaluate the bioequivalence of lornoxicam in healthy volunteers.METHODS A single oral dose of 8 mg reference and test tablets were given to 20 healthy male volunteers according to a randomized crossover design.Plasma concentrations were determined by LC-MS/MS after deproteinized by methanol.The pharmacokinetic parameters were calculated by DAS 2.0.RESULTS The main pharmacokinetic parameters of lornoxicam in test and reference preparations were as follows:Cmax were(782.0±275.1) μg·L-1 and(823.4±256.1) μg·L-1,tmax were(2.8±1.4) h and(2.6±1.4) h,t1/2 were(3.5±1.2) and(3.3±0.8) h,AUC0-24 h were(4 545±1 714) and(4 516±2 054) μg·h·L-1,respectively.The relative bioavailability of lornoxicam was(103.8±15.0) %.CONCLUSION The method was proved to be accurate,sensitive and convenient;lornoxicam in the test tablets was bioequivalent to the reference tablets.