Pharmacokinetics and bioequivalence analysis of amlodipine tablets in Chinese female and male volunteers by HPLC-MS/MS

HPLC-MS/MS法研究氨氯地平片在健康人体内的药动学和生物等效性（英文）

In the present study, we determined the pharmacokinetics and bioequivalence of two amlodipine tablets in Chinese male and female volunteers using HPLC-MS/IVIS method. A randomized, two-period and crossover design was conducted in 20 healthy volunteers （14 male subjects and six female subjects）. A single dose of either the reference or test formulation was given at the start of each period. Blood samples were collected before drug administration and at 1, 2, 3, 4, 5, 6, 8, I0, 12, 24, 48, 72, 96, 120 and 144 h after drug administration. Plasma amlodipine was detected by HPLC-MS/MS method, and the pharmacokinetic parameters were analyzed using DAS 3.2.8. The developed HPLC-MS/MS method was suitable for the analysis of amlodipine in biological matrix samples. The main pharmacokinetic parameters between the trial preparation and the reference preparation met the regulatory criteria for bioequivalence, and the two preparations were both well tolerated.

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。