固相萃取结合HPLC测定血浆中阿替洛尔及其相对生物利用度的研究

DETECTION OF ATENOLOL IN PLASMA BY SPE COMBINED WITH HPLC AND RELATIVE BIOAVAILABILITY OF ATENOLOL TABLETS

目的 :建立血浆中阿替洛尔的固相萃取结合HPLC的检测方法 ;对两厂家生产的阿替洛尔片在人体内的相对生物利用度及生物等效性进行评价。方法 :血样采用固相萃取法处理 ,HPLC 荧光检测法测定 ,外标法定量。生物等效性以AUC0～ 36 、Cmax、Tmax为指标 ,双单侧t检验作判断。结果 :实验制剂与参比制剂的药动学参数AUC0～ 36 、Cmax、Tmax、t1/2 分别为 5 15 0 .3 5± 1172 .5 2、5 4 66.5 0± 12 77.0 8ng·h·ml 1;717.0 4± 189.69、678.63± 193 .3 6ng·ml 1;2 .4 2± 0 .4 5、2 .63± 0 .5 4h ;7.84± 1.2 5、7.73± 1.5 9h。配对t检验结果 ,两厂家产品的AUC0～ 36 、Cmax、Tmax均无显著性差异 (P >0 .0 5 )。结论 :固相萃取结合HPLC法为一种测定血浆阿替洛尔浓度较为理想的方法。两厂家产阿替洛尔片为生物等效制剂 ,试验药物对参比药物相对生物利用度为 94 .2 2 %。

OBJECTIVE:To establish a method to determine atenolol concentration in plasma by SPE HPLC, and to study relative bioavailability of atenolol tablets.METHODS:The atenolol concentrations in plasma through solid phase extraction SFE were determined by HPLC method following a single oral dose were given to 12 volunteers. RESULTS: RSD in a day and between days were less than 10% and recovery rates of plasma coincided for pharmacokinetic study. The pharmacokinetic parameters of xperimental tablets and comparative tablets,AUC 0 36 , C max , T max , t 1/2 were 5 150.35±1 172.52 ng·h·ml 1 and 5 466.50±1 277.08 ng·h·ml 1 ,717.04±189.69 ng·ml 1 and 678.63±193.36 ng·ml 1 , 2.42±0.45 h and 2.63±0.54 h, 7.84±1.25 h and 7.73±1.59 h. There were no significant different between the two formulations in the AUC, T max , C max .CONCLUSION: The SPE HPLC method to determine atenolol concentration is a good method. The two formulations were bioequivalent, the relative bioavailability was 94.22%.