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本文采用高效液相色谱-串联质谱法(HPLC-MS/MS)研究两种氨氯地平片在健康人体内的药动学及生物等效性。采用随机双周期交叉实验设计,20名健康受试者(14名男性,6名女性),每周期单剂量口服10 mg氨氯地平片受试制剂或参比制剂后,于服药前和服药后1、2、3、4、5、6、8、10、12、24、48、72、96、120和144 h各抽取静脉血4 m L。采用优化后的高效液相色谱-串联质谱法(HPLC-MS/MS)测定氨氯地平的血药浓度,用DAS 3.2.8药动学软件求算药动学参数。20名受试者全部完成试验,受试制剂和参比制剂的主要药动学参数如下:t_(max)分别为(5.7±2.4)和(5.3±0.9)h,C_(max)分别为(6.6±1.3)和(6.6±1.9)ng/m L,AUC_(0–144)分别为(281.5±75.9)和(289.3±77.9)ng·h/m L,AUC_(0–∞)分别为(309.3±84.6)和(321.3±88.2)ng·h/m L,t_(1/2)分别为(41.1±11.0)和(43.7±13.7)h。C_(max),AUC_(0–144)和AUC_(0–∞)经对数转换后90%置信区间分别为91.8%–111.2%,94.6%–102.5%,93.9%–101.8%,满足生物等效性分析的要求。整个试验过程中,无严重不良反应发生。本试验建立的HPLC-MS/MS法适用于生物样本的分析。试验制剂和参比制剂的主要药动学参数满足生物等效性分析的要求。
In this paper, HPLC-MS / MS was used to study the pharmacokinetics and bioequivalence of two amlodipine tablets in healthy volunteers. A randomized, two-cycle crossover design was used. Twenty healthy subjects (14 males and 6 females) received a single oral dose of 10 mg amlodipine every week after taking the test or reference formulation. Before and after taking the medicine 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120 and 144 h. The plasma concentration of amlodipine was determined by HPLC-MS / MS. The pharmacokinetic parameters were calculated by DAS 3.2.8 pharmacokinetic software. Twenty test subjects completed the test. The main pharmacokinetic parameters of the test preparations and the reference preparations were as follows: t max was 5.7 ± 2.4 and 5.3 ± 0.9 h respectively, C max was 6.6 ± 1.3 and 6.6 ± 1.9 ng / m L, respectively. The AUC 0-144 values were (281.5 ± 75.9) and (289.3 ± 77.9) ng · h / m L, respectively. 309.3 ± 84.6) and (321.3 ± 88.2) ng · h / m L, respectively. The t 1/2 was 41.1 ± 11.0 and 43.7 ± 13.7 h, respectively. The 90% confidence intervals of C max, AUC 0-144 and AUC 0 -∞ were 91.8% -111.2%, 94.6% -102.5% and 93.9% -101.8% after logarithmic transformation, respectively. Effectiveness analysis requirements. Throughout the experiment, no serious adverse reactions occurred. The HPLC-MS / MS method established in this study is suitable for the analysis of biological samples. The main pharmacokinetic parameters of the test and reference preparations meet the requirements of the bioequivalence analysis.