摘要
目的建立测定人血浆中米非司酮浓度的LC-MS/MS测定方法,并评价米非司酮的药动学特征及2种制剂的人体生物等效性。方法 24名女性健康受试者随机分成2组,分别交叉给予受试制剂和参比制剂,采用LC-MS/MS测定米非司酮的浓度。流动相为甲醇-20 mmol·L-1的醋酸铵水溶液(含0.2%甲酸)(12∶88),柱温:35℃。质谱采用多反应监测模式,检测离子为米非司酮m/z 430.3→372.2,地西泮为m/z 285.1→193.1,评价米非司酮的药动学参数及2种制剂的人体生物等效性。结果人血浆中米非司酮片的最低定量限为10μg·L-1,在10～3000μg·L-1范围内线性关系良好,批内及批间精密度RSD均小于15%。受试制剂与参比制剂的各主要药动学参数:tmax分别为(0.88±0.27)和(0.81±0.42)h,Cmax分别为(1332±373.3)和(1479±388.3)μg·L-1,t 1/2分别为(25.7±8.0)和(25.9±10.0)h,用梯形法计算AUC(0～120h)分别为(16 410±4086)和(16 673±4458)μg·h·L-1;相对生物利用度为114.6%。结论对主要药动学参数进行比较,评价结果显示两种制剂生物等效。
Objective To establish an LC-MS/MS method for the determination of mifepristone in human plasma and to evaluate the pharmacokinetics and bioequivalence of mifepristone hydrochloride tablets in healthy volunteers. Methods A 50 mg dose of the reference or test tablet was given to 24 healthy female volunteers in a randomized two-way crossover design. The plasma concentration of the drug was assayed by LC-MS/MS. Chromatographic separation was carried out on a Spursil C18 column （4.6 mmx 150 mm,5 μm） at 35 ℃, with a mobile phase consisting of methanol-20 mmol ·L^-1 ammonium acetate containing 0.2% formic acid（ 12： 88）. Detection and quantification were performed by mass spectrometry in the multiple reaction monitoring mode with positive electrospray ionization m/z at 430.3→372.2 for mifepristone and 285.1→193.1 for diazepam （internal standard）, respectively. The main pharmacokinetic parameters and bioequivalence of the two formulations were evaluated. Resuits The LOQ of the method for mifepristone in plasma was 10 ng ·ml^-1 and the calibration curve was linear over the range of 10-3000 ng ·ml^-1. The intra-and inter-run standard deviation was less than 15%. The major pharmacokinetic parameters were as follows ： t max （0. 88 ± 0. 27 ） and （0.81 ± 0.42） h, C max （ 1332 ± 373. 3 ） and （ 1479 ± 388.3） μg ·L^-1, t 1/2（25.7 ±8.0） and （25.9 ± 10.0） h, AUC（0.120h）（ 16 410 ±4086） and （ 16 673 ±4458） μg ·h·L^-1 ,respectively. The relative bioavailability of the test product to the reference was 114.6%. Conclusion This method is successfully applied to pharmacokinetic studies. The two formulations are bioequivalent.
出处
《解放军药学学报》
CAS
2012年第5期408-410,414,共4页
Pharmaceutical Journal of Chinese People's Liberation Army
