替拉扎明在家兔体内的代谢研究  

Studies on the Metoblites of Tirapazaming in Rabbits

作　　者：陈红 张丹[2] 杨宇[2] 

机构地区：[1]成都市药品检验所,成都610000 [2]四川大学华西药学院,成都610041

出　　处：《分析化学》2005年第10期1405-1408,共4页Chinese Journal of Analytical Chemistry

摘　　要：进行了替拉扎明(TPZ)在家兔体内的代谢研进行了研究。化学合成了TPZ的去氧代谢物SR4317和SR4330,由HPLC、TLC、MS、1H NMR及IR分析证实,SR4317和SR4330是TPZ经逐步还原的去氧化合物;采用HPLC梯度洗脱法同时测定家兔血浆中TPZ及其代谢物SR4317、SR4330的含量,得到TPZ及其代谢物的均值血药浓度-时间关系曲线。由此可推知,TPZ在家兔体内的代谢途径为还原代谢,即TPZ逐步还原为4位去氧的代谢物SR4317和1、4位去氧的代谢物SR4330。该研究结果可为TPZ在人体内的代谢研究提供参考。The concentration of tirapazamine （TPZ） and its metabolites SR4317 and SR4330 was simultaneously determinecl by gradient reversed phase high preformance liquid chromatography. The biological reductive metabolism route of TPZ could be studied on the mean of plasma concentration-time in rabbit. It was also speculated that TPZ was reduced to SR4317 and SR4330 by their synthesis and analysis of their HPLC, thin layer chromatography, mass spectrometry, ^1HTLC,MS, ^1H-nuclear magnetic resonance and infrared. Based on the mean of plasma concentration and time in vivo and the synthesis route of its metabolite in vitro of TPZ, SR4317 and SR4330, it could be recommended that biological reductive metabolism route of TPZ was reduced to SR4317 and SR4330 with oxygen lost gradually in rabbit.

关 键 词：替拉扎明 代谢物 家兔 体内 HPLC 梯度洗脱法 化学合成 IR分析 同时测定 关系曲线 

分 类 号：R96[医药卫生—药理学]