Lien E A, Solheim E, Kvinnsland S, Ueland P M
Department of Pharmacology and Toxicology, University of Bergen, Norway.
Cancer Res. 1988 Apr 15;48(8):2304-8.
The occurrence of tamoxifen metabolites in bile was investigated in a 57-year-old female patient receiving chronic treatment with tamoxifen. In bile treated with beta-glucuronidase, two major peaks were detected using a chromatographic system developed for the quantitation of tamoxifen metabolites in human serum. One sharp peak coeluted with 4-hydroxy-tamoxifen whereas a second broad peak eluted slightly ahead of tamoxifen and was separated from all major serum metabolites. This latter peak was identified as the cis (about 30%) and trans (about 70%) isomers of 4-hydroxy-N-desmethyltamoxifen. The identification was based on (a) coelution with authentic standard on reversed-phase chromatography and formation of fluorescent material after photoactivation, (b) a molecular ion (M + 1)+ of 374 m/z as determined with liquid chromatography-mass spectrometry, and (c) a fragmentogram identical to that of the authentic standard, as obtained by gas chromatography-mass spectrometry.
在一名接受他莫昔芬长期治疗的57岁女性患者中，对其胆汁中他莫昔芬代谢物的出现情况进行了研究。在用β-葡萄糖醛酸酶处理的胆汁中，使用为定量人血清中他莫昔芬代谢物而开发的色谱系统检测到两个主要峰。一个尖锐峰与4-羟基他莫昔芬共洗脱，而第二个宽峰在他莫昔芬之前稍早洗脱，并且与所有主要血清代谢物分离。后一个峰被鉴定为4-羟基-N-去甲基他莫昔芬的顺式（约30%）和反式（约70%）异构体。该鉴定基于以下几点：(a) 在反相色谱上与真实标准品共洗脱，且光活化后形成荧光物质；(b) 通过液相色谱-质谱法测定的分子离子（M + 1）+为374 m/z；(c) 通过气相色谱-质谱法获得的碎片图与真实标准品的碎片图相同。
