title: An UPLC-MS/MS method for separation and accurate quantification of tamoxifen and its metabolites isomers.
abstract: A selective and accurate analytical method is needed to quantify tamoxifen and its phase I metabolites in a prospective clinical protocol, for evaluation of pharmacokinetic parameters of tamoxifen and its metabolites in adjuvant treatment of breast cancer. The selectivity of the analytical method is a fundamental criteria to allow the quantification of the main active metabolites (Z)-isomers from (Z)'-isomers. An UPLC-MS/MS method was developed and validated for the quantification of (Z)-tamoxifen, (Z)-endoxifen, (E)-endoxifen, Z'-endoxifen, (Z)'-endoxifen, (Z)-4-hydroxytamoxifen, (Z)-4'-hydroxytamoxifen, N-desmethyl tamoxifen, and tamoxifen-N-oxide. The validation range was set between 0.5ng/mL and 125ng/mL for 4-hydroxytamoxifen and endoxifen isomers, and between 12.5ng/mL and 300ng/mL for tamoxifen, tamoxifen N-desmethyl and tamoxifen-N-oxide. The application to patient plasma samples was performed.
authors.affiliation: EA4553, Université Paul Sabatier Toulouse III, Toulouse F-31000, France. Electronic address: cecile.arellano@univ-tlse3.fr.
authors.forename: Cécile
authors.initials: C
authors.lastname: Arellano
authors.affiliation: EA4553, Université Paul Sabatier Toulouse III, Toulouse F-31000, France; Institut Claudius Regaud, IUCT-O, Laboratoire de pharmacologie, 1 Avenue Joliot-Curie, Toulouse F-31059, France.
authors.forename: Ben
authors.initials: B
authors.lastname: Allal
authors.affiliation: Universita Degli Studi Di Genova, Italy.
authors.forename: Anwar
authors.initials: A
authors.lastname: Goubaa
authors.affiliation: Département d'Oncologie Médicale, IUCT-O, 1 Avenue Irène Joliot-Curie, 31059 Toulouse, France; Université Paul Sabatier, Toulouse III, Toulouse F-31000, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Roché
authors.affiliation: EA4553, Université Paul Sabatier Toulouse III, Toulouse F-31000, France; Institut Claudius Regaud, IUCT-O, Laboratoire de pharmacologie, 1 Avenue Joliot-Curie, Toulouse F-31059, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Chatelut
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000097:blood* / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods* / Q000592:standards; D016903:Drug Monitoring / Q000379:methods* / Q000592:standards; D005260:Female; D005602:France; D006801:Humans; D050216:Metabolic Detoxication, Phase I; D012015:Reference Standards; D012042:Registries; D015203:Reproducibility of Results; D020845:Selective Estrogen Receptor Modulators / Q000097:blood* / Q000493:pharmacokinetics; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000097:blood* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D018931:Antineoplastic Agents, Hormonal; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C016601:afimoxifene; C055492:4-hydroxy-N-desmethyltamoxifen; C035830:tamoxifen N-oxide; C028787:N-desmethyltamoxifen
keywords: 4-Hydroxytamoxifen; Endoxifen; Tamoxifen; Tamoxifen-N-oxide; UPLC–MS/MS