非那雄胺片在健康人体内的药动学及生物等效性研究

Pharmacokinetics and Bioequivalence of Finasteride Tablets in Healthy Subjects

目的 :建立人血浆中非那雄胺的HPLC ESI MS测定法 ,以测定志愿者口服非那雄胺片剂 (5mg/片 )后的血药浓度 ,并对受试制剂和参比制剂的生物等效性进行评价。方法 :血浆样品以 0 1mol/L的NaOH碱化后用乙酸乙酯提取 ,进行HPLC ESI MS分析 ,色谱柱为LichrospherC18(5μm ,2 5cm× 4 6mm ) ,流动相为甲醇 10 0 μmol/L醋酸钠水溶液 (86∶14 ) ,内标为醋酸甲羟孕酮 ,检测离子为m/z 3 95(非那雄胺 )、m/z 40 9(内标 ) ,裂解电压为 10 0V。 2 0名健康志愿者交叉口服供试片和参比片 ,剂量均为 5mg。计算主要药动学参数及相对生物利用度 ,以判断生物等效性。结果 :在 0 1～ 2 0 0ng/ml范围内非那雄胺与内标峰面积比值与浓度线性关系良好 ,最低定量限为 0 0 5ng/ml。受试制剂及参比制剂的生物半衰期分别为 4 6± 1 2h和 4 4± 1 1h ,达峰时间分别为3 1± 0 9h和 2 8± 1 2h ,峰浓度分别为 59 4± 17 9ng·ml-1 和 63 6± 2 2 9ng·ml-1 。以AUC0 2 4计算的受试制剂的相对生物利用度为 (96 9± 14 6) %。结论 :本实验建立的分析方法灵敏、准确、简便。统计学结果表明两种制剂生物等效。

AIM:To develop a HPLC-ESI-MS assay for det ermination of finasteride in human plasma and to investigate the pharmacokinetic s and bioequivalence of finasteride tablets(testing tablets and reference table ts) in human. METHOD: After being made alkaline with sodium hydroxide,plasma was extracted with ethy l acetate and separated by HPLC on a reversed-phase C 18 column with a mobil e ph ase of 100 μmol/L ammonium sodium water solution-methanol (16∶84,v/v). L C-ES I MS was performed in the selected ion monitoring (SIM) mode using target ions a t m/z 395 for finasteride and m/z 409 for the internal standard. The fragmental voltage was 100 V. A randomized crossover design was performed in 20 healthy vol u nteers In the study periods,a single 5 mg dose of each tablet was admini st ered to each volunteer RESULT:Calibration curves were linear ov e r the range 0 1～200 ng/ml The limit of quantification for finasteride in pla sma was 0 05 ng/ml The main pharmacokinetic parameters t 1/2 ,t max and c max were 4 6±1 2 h,3 1±0 9 h and 59 4 ± 17 9 ng/ml for the reference tabl et; 4 4±1 1 h,2 8±1 2 h and 63 6±22 9 ng/ml for the test t ablet respective ly The relative bioavalability of the reference tablet was (96 9±14 6)% T he resu lts of variance analysis and two one-sided t-test showed that there was no sign ificant difference between the two formulations in the AUC and c max .CONCLUSION:The assay was proved to be sensitive,accurate and convenient The two formulations were bioequivalent