摘要
目的:建立LC—MS/MS法测定恒河猴血浆中阿普唑仑的浓度,并用于阿普唑仑胃漂浮片的生物等效性分析。方法:采用随机、双周期、自身交叉试验设计,6只恒河猴单剂量口服受试制剂或参比制剂(1.2mg),不同时间点采集的血浆样本经提取.液相色谱-串联质谱法测定血浆样本中阿普唑仑的浓度,并使用DAS2.1软件计算药代动力学参数,评价制剂的生物等效性。结果:阿普唑仑的线性范围为0.4~100ng·mL^-1,定量下限为0.4ng·mL^-1,日内、日间精密度(RSD)均小于15%,准确度(RE)在.4-15%以内。恒河猴单剂量口服受试制剂和参比制剂Cmax分别为(64.75±8.78)、(78.87±6.06)ng·mL^-1,Tmax分别为(4.50±1.22)、(2.17±0.52)h,t1/2分别为(3.51±1.72)、(3.51±1.52)h,AUC0-t分别为(719.93±114.74)、(326.93±66.20)h·ng·mL^-1,相对生物利用度为(233.18±86.82)%。结论:LC—MS/MS方法适用于阿普唑仑制剂生物等效性研究。受试制剂与参比制剂比较生物利用度显著提高,Tmax显著推迟,具有缓释的效果。
Objective:To establish a method of high performance liquid chromatography tandem mass spectrometry ( HPLC - MS/MS) for the determination of alprazolam in plasma of rhesus monkeys and the bioequivalence analysis of intragastric floating alprazolam tablets. Methods: In a randomized, double - period, self - crossover study, 6 rhe- sus monkeys were given a single oral dose of test or reference tablets containing 1.2 mg alprazolam. Then the plas- ma concentration was determined by HPLC - MS/MS method after extraction of alprazolam. The pharmacokinetie parameters were calculated by DAS 2. 1 program and the bioequivalence of two formulations was evaluated. Results: The calibration curve of alprazolam was linear in the range of 0. 4 - 100 ng · mL-1. The lower limit of quantitation was 0.4 ng · mL-1. Intra - day and inter - day RSDs were both less than 15% and the relative error (RE) was within + 15%. The pharmacokinetic parameters for test tablets vs reference tablets were as follows: Cmax of(64. 75 ±8.78) and(78. 87 ±6.06)ng · mL^-1 ,Tmax of(4.50 ± 1.22)and(2. 17 ±0.52)h,t1/2 of(3.51 ± 1.72) and(3.51 ± 1.52)h,AUC0-t of(719.93 ± 114.74) and(326.93±66.20)h ·ng · ml^ -1 ,the relative hioavailability was(233.18 ± 86.82)%. Conclusion: The LC - MS/MS method is suitable for the bioequivalence study of al- prazolam preparations. The statistic data showed that Tmax for test tablets was significantly delayed eomparded with reference tablets, indicating that test tablets had sustained -release effect.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2014年第3期511-515,共5页
Chinese Journal of Pharmaceutical Analysis
关键词
阿普唑仑
胃漂浮片
缓释制剂
液相色谱-串联质谱法
生物等效性
生物利用度
alprazolam
intragastric floating tablet
sustained release preparation
HPLC - MS/MS
bioequiavailabili-ty
bioavailability