Abstract
This study describes the application of LC/MS/MS to the determination of phase I and phase II metabolites of tamoxifen in urine and plasma samples of breast cancer patients. In the plasma extracts, in addition to the parent drug and N-desmethyltamoxifen, a minor metabolite tamoxifen N-oxide was identified for the first time in human. Four intact glucuronides of tamoxifen metabolites were isolated in the 24-hr posttreatment urine sample. They were the glucuronides of 4-hydroxytamoxifen, 4-hydroxy-N-desmethyltamoxifen, dihydroxytamoxifen, and a monohydroxy-N-desmethyltamoxifen. Hydroxylation followed by glucuronidation is a well-established metabolic route of tamoxifen, and this study describes for the first time direct analyses of these metabolites in human urine samples using on-line LC tandem MS.
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