title: Importance of highly selective LC-MS/MS analysis for the accurate quantification of tamoxifen and its metabolites: focus on endoxifen and 4-hydroxytamoxifen.
abstract: The antiestrogenic effect of tamoxifen is mainly attributable to the active metabolites endoxifen and 4-hydroxytamoxifen. This effect is assumed to be concentration-dependent and therefore quantitative analysis of tamoxifen and metabolites for clinical studies and therapeutic drug monitoring is increasing. We investigated the large discrepancies in reported mean endoxifen and 4-hydroxytamoxifen concentrations. Two published LC-MS/MS methods are used to analyse a set of 75 serum samples from patients treated with tamoxifen. The method from Teunissen et al. (J Chrom B, 879:1677-1685, 2011) separates endoxifen and 4-hydroxytamoxifen from other tamoxifen metabolites with similar masses and fragmentation patterns. The second method, published by Gjerde et al. (J Chrom A, 1082:6-14, 2005) however lacks selectivity, resulting in a factor 2-3 overestimation of the endoxifen and 4-hydroxytamoxifen levels, respectively. We emphasize the use of highly selective LC-MS/MS methods for the quantification of tamoxifen and its metabolites in biological samples.
authors.affiliation: Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands. Nynke.Jager@slz.nl
authors.forename: N G L
authors.initials: NG
authors.lastname: Jager
authors.forename: H
authors.initials: H
authors.lastname: Rosing
authors.forename: S C
authors.initials: SC
authors.lastname: Linn
authors.forename: J H M
authors.initials: JH
authors.lastname: Schellens
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000737:chemistry / Q000378:metabolism*; D002853:Chromatography, Liquid; D006801:Humans; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; C016601:afimoxifene; C055492:4-hydroxy-N-desmethyltamoxifen