ANALYSIS OF PHASE-I AND PHASE-II METABOLITES OF TAMOXIFEN IN BREAST-CANCER PATIENTS

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 s amples of breast cancer patients. In the plasma extracts, in addition to the parent drug and N-desmethyltamoxifen, a minor metabolite tamoxi fen N-oxide was identified for the first time in human. Four intact gl ucuronides of tamoxifen metabolites were isolated in the 24-hr posttre atment 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 describe s for the first time direct analyses of these metabolites in human uri ne samples using on-line LC tandem MS.