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目的:建立人血浆中米格列奈浓度的LC-MS/MS检测方法,研究米格列奈钙片单次及连续给药后在健康人体内的药代动力学。方法:应用建立的LC-MS/MS法测定人血浆米格列奈浓度,以DAS软件计算主要药代动力学参数。结果:健康受试者单次给药5,10,20 mg主要药代动力学参数:Cmax为(435.3±182.5),(811.7±276.0)和(1 549.8±353.2)μg.L-1;Tmax为(0.642±0.61),(0.508±0.29)和(0.5±0.167)h;t1/2为(1.445±0.146),(1.343±0.215)和(1.404±0.209)h;AUC0~t为(725.7±154.8),(1 504.3±285.3)和(2 784.9±554.0)μg.L-1.h。连续给药10 mg主要药代动力学参数:Cmax为(1 005.7±338.0)μg.L-1;Tmax为(0.492±0.384)h;Cmin为(40.33±20.15)μg.L-1;t1/2为(1.670±0.363)h;AUCss为(1 645.2±469.1)μg.L-1.h;Cav为(205.6±58.64)μg.L-1;DF(4.670±0.974)。结论:本方法灵敏度高,无杂质干扰,适用于人体药代动力学研究。米格列奈钙片单次口服5~20 mg剂量范围内,体内过程呈线性;连续给药7 d,血药浓度d4已达稳态,体内无蓄积。
OBJECTIVE: To establish a LC-MS / MS method for the determination of mitiglinide in human plasma and to study the pharmacokinetics of mitiglinid in healthy volunteers after single or continuous administration. Methods: The plasma concentrations of mitiglinide were determined by LC-MS / MS. The main pharmacokinetic parameters were calculated by DAS software. RESULTS: The main pharmacokinetic parameters of 5,10,20 mg for healthy subjects were: Cmax (435.3 ± 182.5), (811.7 ± 276.0) and (5449.8 ± 353.2) μg.L-1, respectively; Tmax Were (0.642 ± 0.61), (0.508 ± 0.29) and (0.5 ± 0.167) h respectively; t1 / 2 was 1.445 ± 0.146, 1.343 ± 0.215 and 1.404 ± 0.209 h, AUC0-t was (725.7 ± 154.8), (1 504.3 ± 285.3) and (2 784.9 ± 554.0) μg.L-1.h. The main pharmacokinetic parameters of continuous administration of 10 mg were as follows: Cmax was (1005.7 ± 338.0) μg.L-1, Tmax was (0.492 ± 0.384) h, Cmin was (40.33 ± 20.15) μg.L- 2 was (1.670 ± 0.363) h; AUCss was (1645.2 ± 469.1) μg.L-1.h; Cav was (205.6 ± 58.64) μg.L-1; DF was 4.670 ± 0.974. Conclusion: The method has high sensitivity and no impurity interference and is suitable for human pharmacokinetic studies. The dose of mitochondria in a single oral dose ranged from 5 to 20 mg, and the in vivo process was linear. After continuous administration for 7 days, the plasma concentration of d4 reached a steady state without accumulation in the body.