Norman R L, Wood A W
Drug Metab Dispos. 1984 Sep-Oct;12(5):543-9.
A novel metabolite of coumarin was isolated by high pressure liquid chromatography from in vitro incubations with a rat liver 10,000g postmitochondrial supernatant fraction. Mass spectral analysis and co-chromatography with authentic reference compound was utilized to identify the lactone ring-opened metabolite as o-hydroxyphenylethanol. Formation of this metabolite required both the microsomal and cytosolic fractions and the maximum rate of production was observed in the presence of both NADPH and NADH. Analysis of urine from rats administered [14C]coumarin established that o-hydroxyphenylethanol was formed in vivo and the amount excreted was about 15% of that of o-hydroxyphenylacetic acid, the major urinary metabolite. Precursor-product relationship studies indicated that o-hydroxyphenylethanol was readily converted to o-hydroxyphenylacetic acid both in vivo and in vitro while the reverse reaction was not observed. The relationships of these results to the currently accepted pathway(s) leading to ring-opened coumarin products are discussed.
通过高压液相色谱法，从大鼠肝脏10,000g线粒体后上清液组分的体外孵育物中分离出一种新型香豆素代谢物。利用质谱分析以及与标准参考化合物的共色谱法，将内酯环开环代谢物鉴定为邻羟基苯乙醇。该代谢物的形成需要微粒体和胞质溶胶组分，并且在同时存在NADPH和NADH的情况下观察到最大生成速率。对给予[14C]香豆素的大鼠尿液分析表明，邻羟基苯乙醇在体内形成，排泄量约为主要尿液代谢物邻羟基苯乙酸的15%。前体-产物关系研究表明，邻羟基苯乙醇在体内和体外都很容易转化为邻羟基苯乙酸，而未观察到反向反应。讨论了这些结果与目前公认的导致香豆素开环产物的途径之间的关系。
