阿司匹林肠溶片生物等效性试验

目的:测定健康男性受试者口服单剂量阿司匹林肠溶片(受试制剂)与市售阿司匹林(参比制剂)血浆中水杨酸的浓度,研究受试制剂与参比制剂的吸收速度、吸收程度和体内的相对生物利用度,评价受试制剂与参比制剂是否具有生物等效性。方法:采用双周期随机交叉设计,液相色谱-质谱联用法(HPLC-MS)测定血浆中阿司匹林的有效代谢物水杨酸的药物浓度。HPLC-MS条件:采用MG PAKC₁₈色谱柱(150 mm×2.0 mm,5.0 μm),以乙腈(含0.1%甲酸)-水(含0.1%甲酸)(70:30)为流动相,流速0.3 mL·min^-1。负离子选择反应方式监测;水杨酸反应离子m/z 137.0→93.1;内标(硝西泮)反应离子m/z 280.0→252.0。用DAS 2.1.1药动学软件进行评价。结果:2种制剂水杨酸的AUC_0-t和C_max均拒绝生物不等效假设。受试制剂AUC_0-t的90%置信区间为参比制剂相应参数的96.6%~112.9%;C_max的90%置信区间为参比制剂相应参数的93.2%~112.2%,均落在等效范围内。水杨酸的T_max经非参数秩和检验,两制剂T_max的差异无统计学意义。结论:2种制剂在体内具有生物等效性。

Objective:To determine the concentration of salicylic acid in healthy male subjects plasma between the aspirin enteric-coated tested preparation and the reference preparation,study the relative bioavailability in vivo,including absorption rate and degree of absorption,and evaluate the bioequivalence of preparations and reference subjects.Methods:The salicylic acid concentration of aspirin effective metabolites in plasma was determined through double random cross test cycle.The samples were chromatographed on a MG PAK-C₁₈ column(150 mm×2.0 mm,5.0 μm)using a mobile phase consisting of acetonitrile(0.1% formic acid) and water(0.1% formic acid)(70:30)at the flow rate of 0.3 mL·min^-1.The negative ions of analytes were detected in negative ionization in selective reaction monitoring mode(SRM).The mass transition pairs of m/z 137.0→93.1,m/z 280.0→252.0 were used to detect Salicylic acid and Nitrate diazepam(internal standard).Use the DAS 2.1.1 pharmacokinetic software evaluation.Results:None of the two formulations of salicylic acid AUC_0-t and C_max were rejected by bioequivalence hypothesis;AUC_0-t 90% confidence interval of the test formulation was 96.6%-112.9% for the reference formulation of the corresponding parameters;C_max 90% confidence interval of the test formulation was 93.2%-112.2% for the reference formulation of the corresponding parameters,which fells within the equivalent scope.Salicylic acid tmax was tested by nonparametric rank sum test,and differences between the two formulations T_max was not statistically significant.Conclusion:The two formulations are bioequivalent in vivo.