阿尼西坦缓释片体内代谢产物的测定及药代动力学研究  

Determination of metabolites in vivo for aniracetam sustained release tablet and pharmacokinetic study

作　　者：李连坤[1] 张蕾[1] 王甜甜[1] 王雪[1] 张雯娜[1] 蔡广知[1] 贡济宇[1] 

机构地区：[1]长春中医药大学,长春130117

出　　处：《中国当代医药》2016年第6期8-10,14,共4页China Modern Medicine

基　　金：吉林省科技发展计划项目(20110434)

摘　　要：目的建立阿尼西坦缓释片体内代谢产物N-对甲氧基苯甲酰氨基丁酸(ABA)含量的测定方法。方法采用反相高效液相色谱法(HPLC法)测定ABA含量,PhenomenexΜP-ODS C18色谱柱(250×4.6 mm,5μm),流动相:乙腈∶0.1%醋酸=25∶75,检测波长:250 nm,柱温:35℃。结果以氯仿∶甲醇为2∶8,涡旋振荡30 s,离心10 min,于40℃下氮气吹干处理血样。在67.5～2150μg/L范围内线性关系良好,回收率为86.67%～93.58%,均在85%以上,符合实验要求。主要药代动力学参数为:阿尼西坦缓释片的AΜC0-t为(342.13±110.23)μg/(min·ml),Cmax为(7.41±2.05)μg/ml,Tmax为(116.53±1.17)h;阿尼西坦普通片的AΜC0-t为(434.53±102.69)μg/(min·ml),Cmax为(7.46±1.87)μg/ml,Tmax为(28.29±1.11)h。结论本实验建立的HPLC法,可以准确测定阿尼西坦体内代谢产物ABA的含量,适用于阿尼西坦缓释片在家兔体内的药代动力学研究。Objective To establish the determination method of N-anisoyl-GABA(ABA) content of metabolites in vivo for aniracetam sustained release tablet. Methods The content of ABA was determined by reversed-phase high performance liquid chromatography(RP-HPLC method).Phenomenex ΜP-ODS C18 chromatographic column(250×4.6 mm,5 μm)was used and the mobile phase was set as acetonitrile∶0.1% acetic acid =25∶75,detection wavelength was set at 250 nm,and column temperature was 35℃. Results The blood sample were blow-dried by nitrogen at 40℃(chloroform∶methyl alcohol=2∶8,vortex oscillation for 30 s and centrifugation for 10 min).The result showed favorable linear relation in range of 67.5～2150 μg/L.The recovery rate was 86.67%-93.58%,meeting the experiment requirements of above 85%.The main pharmacokinetic parameters was as follows:the aniracetam sustained release tablet,AΜC_(0-t)=(342.13±110.23) μg/(min·ml),C_max=(7.41±2.05) μg/ml,and Tmax=(116.53±1.17) h;the aniracetam conventional tablet,AΜC_(0-t)=(434.53±102.69) μg/(min·ml),C_max=(7.46±1.87) μg/ml,and Tmax=(28.29±1.11) h. Conclusion HPLC method established in this study can accurately determine the ABA content of metabolites in vivo for aniracetam,which is applicable to pharmacokinetic study of aniracetam sustained release tablet in rabbits in vivo.

关 键 词：阿尼西坦 N-对甲氧基苯甲酰氨基丁酸 反相高效液相色谱法 血药浓度 药代动力学 

分 类 号：R284.2[医药卫生—中药学]