title: Identification and mechanism of formation of potentially genotoxic metabolites of tamoxifen: study by LC-MS/MS.
abstract: On-line high-performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI MS) and tandem mass spectrometry (MS/MS) have been applied to the study of tamoxifen metabolism in liver microsomes and to the identification of potentially genotoxic metabolites. The results showed that the hydroxylated derivatives, including 4-hydroxytamoxifen and alpha-hydroxytamoxifen are detoxication metabolites, while arene oxides, their free radical precursors or metabolic intermediates, are the most probable species involved in DNA-adduct formation.
authors.affiliation: MRC Toxicology Unit, University of Leicester, UK.
authors.forename: C K
authors.initials: CK
authors.lastname: Lim
authors.forename: Z X
authors.initials: ZX
authors.lastname: Yuan
authors.forename: R M
authors.initials: RM
authors.lastname: Jones
authors.forename: I N
authors.initials: IN
authors.lastname: White
authors.forename: L L
authors.initials: LL
authors.lastname: Smith
mesh_terms: D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts; D004249:DNA Damage; D004965:Estrogen Antagonists / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D013058:Mass Spectrometry / Q000379:methods*; D008862:Microsomes, Liver / Q000378:metabolism*; D015394:Molecular Structure; D009153:Mutagens / Q000378:metabolism*; D013629:Tamoxifen / Q000378:metabolism*
chemical_list: D018736:DNA Adducts; D004965:Estrogen Antagonists; D009153:Mutagens; D013629:Tamoxifen