Identification and mechanism of formation of potentially genotoxic metabolites of tamoxifen: study by LC-MS/MS.
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.
Lim
C K
CK
MRC Toxicology Unit, University of Leicester, UK.
Yuan
Z X
ZX
Jones
R M
RM
White
I N
IN
Smith
L L
LL
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*
D018736:DNA Adducts; D004965:Estrogen Antagonists; D009153:Mutagens; D013629:Tamoxifen