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建立了液相色谱-串联质谱法测定人血浆中的伊马替尼,计算甲磺酸伊马替尼胶囊受试和参比制剂在健康志愿者体内的药动学,并评价两制剂的生物等效性。使用Thermo BDS C18色谱柱,乙腈∶0.2%甲酸(含20 mmol/L乙酸铵)(88∶12)为流动相;质谱采用电喷雾离子源,正离子多反应监测(MRM)模式,监测离子对为m/z 494.3→m/z 394.2(伊马替尼)和m/z 394.2→m/z 278.1(厄洛替尼,内标)。采用双周期、随机、自身交叉试验设计,36名男性健康志愿者分别口服受试或参比制剂400 mg。计算得受试和参比制剂的主要药动学参数如下:cmax(1 854±592)、(1 865±606)ng/ml,tmax(4.0±1.0)、(4.4±1.4)h,t1/2(13.1±2.4)、(12.7±1.8)h,AUC0→t(29 783±12 514)、(30 376±14 323)ng·h·ml-1。结果显示两制剂生物等效。
A liquid chromatography-tandem mass spectrometry was developed for the determination of imatinib in human plasma. The pharmacokinetics of imatinib mesylate capsules and reference preparations in healthy volunteers were calculated, and the bioactivity of the two preparations was evaluated Equivalence. Acetonitrile: 0.2% formic acid (containing 20 mmol / L ammonium acetate) (88:12) was used as the mobile phase on a Thermo BDS C18 column. The mass spectra were monitored by electrospray ionization, positive ion multiple reaction monitoring (MRM) M / z 494.3 → m / z 394.2 (imatinib) and m / z 394.2 → m / z 278.1 (erlotinib, internal standard). Using a two-cycle, randomized, crossover trial design, 36 healthy volunteers were orally administered 400 mg of the test or reference formulation, respectively. The main pharmacokinetic parameters were calculated as follows: cmax (1 854 ± 592), (1865 ± 606) ng / ml, tmax 4.0 ± 1.0, 4.4 ± 1.4 h, t1 / 2 (13.1 ± 2.4), (12.7 ± 1.8) h, AUC0 → t (29 783 ± 12 514), (30 376 ± 14 323) ng · h · ml-1. The results show that both formulations are bioequivalent.