【摘要】 目的:建立一种测定人体血浆中格列本脲浓度的高效液相色谱法,并对供试制剂与参比制剂的生物等效性进行评价。方法:血样处理采用固相萃取方法,萃取小柱用甲醇活化后加入血浆1.5mL 及内标地西泮溶液20μL,过柱后用含20%甲醇的水溶液1.0mL 洗涤,洗涤液弃去,再用甲醇1.0mL 洗脱收集,收集液于60℃水浴挥干,最后用甲醇100μL溶解,取20μL进样。色谱条件:色谱柱为 ODS C₁₈柱（4.6mm×150mm,5μm）;流动相为0.01moL·L^-1磷酸二氢钾溶液（用磷酸调 pH 为6.1）-乙腈（43∶57）;流速为1.0mL·min^-1;荧光检测波长为λ_ex=235nm,λ_em=354nm。人体药代动力学试验采用双周期交叉设计方案,将18名志愿受试者随机分为两组,分别口服格列本脲供试片和参比片2.5mg。结果:本方法线性范围为2～128ng·mL^-1,r=0.9991,最低检测限为2ng·mL^-1,方法回收率为97.6%～98.5%,日内、日间 RSD 均小于10%,供试制剂与参比制剂主要药代动力学参数经统计学分析无显著性差异。结论:本方法灵敏度高,特异性强,重复性好,供试制剂与参比制剂具有生物等效性。更多还原

【Abstract】 Objective:To develop an HPLC-fluorescence method for the study of pharmacokinetics and bioavail- ability of glibenclamide in male volunteers.Method:1.5 mL plasma sample spiked with diazepam（internal stand- ard）were applied to C₁₈ cartridges.After washing with water（include 20% methanol）,the cartridge was eluted with methanol.The eluate was evaporated to dryness at 60℃.The residue was dissolved in methanol and injected to a Diamonsil ODS C₁₈ column（4.6 mm×150 mm,5μm）.The mobile phase was 0.01 mol·L^-1 KH₂ PO₄ solution （pH=6.1 ,adjusted with H₃ PO₄）-acetonitrile（43:57）.The flow rate was 1.0 mL·min^-1.A fluorescence detec- tor was set at 235 nm excitation wavelength and 354 nm emission wavelength to monitor eluted components.A single oral dose of 2.5 mg of test tablets or reference tablets was given to each 18 volunteers in an open randomized two- way crossover design.Result:The linear range was 2-128 ng·mL^-1,r=0.9991.The limit of determination was 2 ng·mL^-1.The method recovery was 97.6%-98.5%.Within-day precision（RSD）and between-day precision （RSD）were less than 10%.The main pharmacokinetic parameters obtained showed no statistically significant differ- ence between two preparations.Conclusion:The method is sensitive,specific and reproducible for the determination of glibenclamide concentration in human plasma.Two products was bioequivalent.更多还原