Determination of tamoxifen and an hydroxylated metabolite in plasma from patients with advanced breast cancer using gas chromatography-mass spectrometry.

An assay has been established for the selective measurement of tamoxifen and its monohydroxy derivative, metabolite B, in human plasma. The assay was used to examine the concentrations of these compounds, relative to oestradiol-17 beta, in the plasma of patients undergoing tamoxifen therapy for advanced breast cancer. Oral administration of the drug (20 mg twice a day) raised the level of tamoxifen in plasma to approximately 200 ng/ml 20 days after the commencement of treatment. This level was 3000-fold higher than the corresponding concentration of oestradiol which remained within the range for post-menopausal women. Metabolite B was present in plasma at a much lower concentration than tamoxifen although in considerable excess over oestradiol. The overall results are discussed in relation to the possible mechanism of action of the drug.