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 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.
Poon
G K
GK
Drug Development Section, Institute of Cancer Research, Sutton, Surrey, UK.
Chui
Y C
YC
McCague
R
R
Lłnning
P E
PE
Feng
R
R
Rowlands
M G
MG
Jarman
M
M
D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D013629:Tamoxifen / Q000097:blood / Q000378:metabolism* / Q000652:urine
D013629:Tamoxifen