Analysis of tamoxifen and 4-hydroxytamoxifen levels in immature rat uterine cytoplasm and KCl-nuclear extracts by gas chromatography-mass spectrometry (GC-MS) using selected ion monitoring (SIM).
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.
Murphy
C
C
Department of Pharmacology, University College Dublin, Republic of Ireland.
Fotsis
T
T
Adlercreutz
H
H
Martin
F
F
D000818:Animals; D003600:Cytosol / Q000378:metabolism; D004965:Estrogen Antagonists / Q000493:pharmacokinetics*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D051381:Rats; D011919:Rats, Inbred Strains; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D014316:Tritium; D014599:Uterus / Q000378:metabolism*
D004965:Estrogen Antagonists; D013629:Tamoxifen; D014316:Tritium; C016601:afimoxifene