液相色谱-串联质谱法测定人血浆中格列喹酮及其2种片剂的生物等效性研究

目的: 建立测定人血浆中格列喹酮的液相色谱-串联质谱法,并用于其2种片剂的生物等效性研究。 方法: 采用随机、双周期、自身交叉试验设计,22名健康男性受试者单剂量口服受试制剂或参比制剂(给药剂量30 mg),所采集的人血浆样本经沉淀蛋白,液相色谱-串联质谱法测定人血浆中格列喹酮的浓度,并使用DAS2.1.1软件计算药代动力学参数,评价2种制剂的生物等效性。 结果: 格列喹酮的线性范围为10.0~1000 ng·mL^-1,批内、批间精密度(RSD)均小于15%,准确度(RE)在±15%以内。受试制剂与参比制剂的AUC_0-t分别为(2717.0±685.6)和(2719.7±744.2)ng·h·mL^-1;C_max分别为(510±202)和(514±185)ng·mL^-1;T_max分别为(3.5±1.0)和(3.7±1.1)h;t_1/2分别为(5.9±5.5)和(6.9±6.4)h。以AUC_0-t计,受试制剂的相对生物利用度为(102.1±18.3)%。 结论: 该方法简单、灵敏、专属,适用于格列喹酮口服制剂的人体生物等效性研究。统计结果表明受试制剂和参比制剂具有生物等效性。

Objective: To develop a liquid chromatographic-mass spectrometric(LC-MS/MS)method for the determination of gliquidone in human plasma and evaluate the bioequivalence of its two tablets. Methods: In a randomized,double-period,self-crossover study,22 healthy male subjects received a single oral dose of test or reference formulation containing 30 mg gliquidone.Gliquidone in plasma was determined by the LC-MS/MS method after precipitation of protein.The main pharmacokinetic parameters were calculated by software DAS 2.1.1.and the bioequivalence of two formulations was evaluated. Results: The linear calibration curve was obtained over the concentration range of 10.0-1000 ng·mL^-1.The intra-and inter-batch relative standard deviation(RSD)were both less than 15% and the relative error(RE)was within±15%.The main pharmacokinetic parameters of test formulation and reference formulation were as following:AUC_0-t were(2717.0±685.6)and(2719.7±744.2)ng·h·mL^-1;C_max were (510±202) and (514±185)ng·mL^-1;T_max were (3.5±1.0)and(3.7±1.1)h;t_1/2 were(5.9±5.5)and(6.9±6.4)h,respectively.By calculation of AUC_0-t,the relative bioavailability of test formulation was(102.1±18.3)%. Conclusion: The method was simple,sensitive,specific and suitable for the bioequivalence study of gliquidone oral formulations in human.The statistic data showed that the test formulation and reference formulation had the similar rate and extent of absorption,and they were bioequivalent.