RT Journal Article
SR Electronic
T1 Identification of tamoxifen metabolites in human Hep G2 cell line, human liver homogenate, and patients on long-term therapy for breast cancer.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 377
OP 382
VO 23
IS 3
A1 G K Poon
A1 B Walter
A1 P E Lønning
A1 M N Horton
A1 R McCague
YR 1995
UL http://dmd.aspetjournals.org/content/23/3/377.abstract
AB The metabolism of tamoxifen was examined in human liver homogenate and human Hep G2 cell line preparations by LC/electro spray ionization/MS. Several metabolites were detected in the human liver homogenate extracts, namely N-didesmethyltamoxifen (metabolite I), alpha-hydroxytamoxifen (metabolite II), 4-hydroxytamoxifen (metabolite III), N-desmethyltamoxifen (metabolite IV), and tamoxifen N-oxide (metabolite V). Metabolites II, III, IV, and V were observed in the samples after incubating tamoxifen with the human Hep G2 cell line. When these results were compared with the metabolic profiles in patients, apart from metabolites I-V, alpha-hydroxy-N-desmethyltamoxifen (VI) and 4-hydroxy N-desmethyltamoxifen (VII) were present in all the plasma samples. In addition, in patients who had received tamoxifen treatment daily for > 6 months, several minor metabolites were detected, namely 4-hydroxytamoxifen N-oxide (metabolite VIII) and two dihydroxylated analogs (metabolites IX and X). The precise positions of the hydroxylation have yet to be determined.