Identification of 4-hydroxy-N-desmethyltamoxifen as a metabolite of tamoxifen in human bile.
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.
Lien
E A
EA
Department of Pharmacology and Toxicology, University of Bergen, Norway.
Solheim
E
E
Kvinnsland
S
S
Ueland
P M
PM
D001646:Bile / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D008875:Middle Aged; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*
D013629:Tamoxifen; C055492:4-hydroxy-N-desmethyltamoxifen