体外试验中HPLC同时测定茶碱及其代谢物的研究

SIMULTANEOUS DETERMINATION OF THEOPHYLLINE AND ITS METABOLITES BY HPLC IN DRUG DRUG INTERACTION IN VITRO STUDY

用高效液相色谱法（ Ｈ Ｐ Ｌ Ｃ）同时测定体外试验中经大鼠肝药酶 Ｐ４５０ 代谢的茶碱代谢物，以及受依诺沙星和左氟诺沙星抑制后的茶碱代谢物的含量变化。讨论了 Ｅ Ｎ Ｘ、 Ｌ Ｖ Ｘ 与茶碱的相互作用。方法的精密度 Ｒ Ｓ Ｄ 为（３２～４６）％ 、回收率为（８５～９２）％ 和最低检测限 ０５ ｎｇ。线性范围（００２～１０）μｇ／ｍ ｌ，ｒ＞ ０９９９９，该法可用于研究药物相互作用中评定茶碱及其代谢物的变化。

A rapidly simultaneous deter mination of theophylline and its four main metabolites produced with hepatic microsomes by high performance liquid chromatography was discussed. Four metabolites:3 methylxanthine, 1 methylxanthine,1 methylurine acid and 1,3 dimethyluric acid with acetaminophen(internal standard) and theophylline were separated within 17 minutes by isocratic HPLC assay. Lower pH(2.62) and some strong formic acid was used. The limited of quantification was 0.5ng and the analytical precision and recovery were 3.2~4.6% and 85~92% respectively. The linear relationship was obtained for each of the metabolites over the concentration range of 0.02~10ug/ml, r >0 999.It is a good method to be used to assess drug interaction involving alternations in the bio transformation of theophylline.