HPLC-MS研究格列吡嗪片人体药动学和生物等效性

 目的建立准确、灵敏的HPLC-MS测定格列吡嗪片在血浆中的浓度,研究格列吡嗪片在健康人体中的药动学及生物等效性。方法18名健康男性受试者单次po 10 mg格列吡嗪片受试制剂和参比制剂后,按规定时间采集肘静脉血,经液-液萃取处理后选用Kromasil C₁₈分析柱(4.6 mm×150 mm,5μm);甲醇-水-甲酸(75∶25∶0.625)为流动相,采用LC-MS测定格列吡嗪的血药浓度,并计算两制剂的主要药动学参数及相对生物利用度。结果测定血浆中格列吡嗪的最低检测限为20μg·L^-1,在20～5 000μg·L^-1内线性关系良好;血药浓度测定的日内、日间精密度RSD均小于10%,测得格列吡嗪受试制剂和参比制剂的主要药动学参数t_max分别为(2.4±0.9)和(2.1±1.0)h,ρ_max分别为(1.2±0.3)和(1.3±0.4)mg·L^-1,t_1/2分别为(5.6±2.2)和(5.1±1.6)h,AUC_0-t分别为(7.6±2.9)和(7.5±3.1)mg·h·L^-1,AUC_0-∞分别为(8.4±3.3)和(8.1±3.3)mg·h·L^-1,受试制剂的相对生物利用度为(102.3±23.7)%。结论建立的HPLC-MS灵敏,准确;测定结果经统计学分析,表明格列吡嗪两种片剂生物等效。

Study on Pharmacokinetics and Bioequivalence of Glipizide Tablets by HPLC-MS in Healthy Volunteers

OBJECTIVE To develop an accurate and sensitive HPLCMS method for determining glipizide in human plasma and to study pharmacokinetics and relative bioavailability of glipizide in healthy Chinese volunteers. METHODS A single oral dose of 10 mg tested or standard glipizide tablets was given to 18 healthy volunteers in a randomized crossover study.Glipizide concentration in plasma was determined by LC-MS after liquid-liquid extraction.A reversed phase C₁₈ column(Kromasil,4.6 mm×150 mm,5 μm)was used and the mobile phase was methanol-water-formic acid(75∶25∶0.625).The pharmacokinetics and bioavailability were studied.RESULTS The detection limit of glipizide in plasma was 20 μg·L^-1 and a good lineaity was obtained over the range of 20～5 000 μg·L^-1.The relative standard deviation of with-day and between-day was less 10%.The pharmacokinetics parameters of tested and standard formulations: t_max(2.4±0.9) and(2.1 ±1.0) h,ρ_max(1.2±0.3) and(1.3 ±0.4) mg·L^-1,t_1/2(5.6 ±2.2) and(5.1 ±1.6) h,AUC_0～t(7.6±2.9) and(7.5±3.1) mg·h·L^-1,AUC_0～∞(8.4 ±3.3) and(8.1±3.3) mg·h·L^-1,the relative bioavailability of tested to stardand tablets was(102.3±23.7)%.CONCLUSION The results demonstrate that two preparations are bioequivalent.