A GC-MS (SIM) method has been developed which allows the measurement of tamoxifen and its metabolites in uterine cytosol and 0.5 M KCl-extracts of uterine nuclei from groups of immature rats. The method was shown to be specific, precise and accurate. Using this procedure tamoxifen and 4-hydroxytamoxifen were tentatively identified and measured in uterine extracts after tamoxifen administration. When tamoxifen and 4-hydroxytamoxifen levels in uterine cytosol and 0.5 M KCl nuclear extracts were compared a relative enrichment in the nuclear fraction of 4-hydroxytamoxifen (relative to tamoxifen) was consistently seen. These observations are supportive of a role for 4-hydroxytamoxifen in mediating the antiestrogenic actions of tamoxifen in the immature rat uterus. In some of the uterine cytosolic fractions desmethyltamoxifen and metabolite Y could also be detected.
Bibliographical noteM1 - 3
Murphy, C Fotsis, T Adlercreutz, H Martin, F Research Support, Non-U.S. Gov't England Journal of steroid biochemistry J Steroid Biochem. 1987 Sep;28(3):289-99.
- Animals Cytosol/metabolism Estrogen Antagonists/*pharmacokinetics Female Gas Chromatography-Mass Spectrometry/methods Rats Rats, Inbred Strains Tamoxifen/*analogs & derivatives/*pharmacokinetics Tritium Uterus/*metabolism