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

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

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。

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 LCMS/MS after deproteinized by methanol. The pharmacokinetic parameters were calculated by DAS 2.0. RESUL＇IS 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, AUC0-24h 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.