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J Pharm Biomed Anal. 2014 Nov;100:254-261. doi: 10.1016/j.jpba.2014.07.033. Epub 2014 Aug 4.

An UPLC-MS/MS method for separation and accurate quantification of tamoxifen and its metabolites isomers.

Author information

1
EA4553, Université Paul Sabatier Toulouse III, Toulouse F-31000, France. Electronic address: cecile.arellano@univ-tlse3.fr.
2
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.
3
Universita Degli Studi Di Genova, Italy.
4
Département d'Oncologie Médicale, IUCT-O, 1 Avenue Irène Joliot-Curie, 31059 Toulouse, France; Université Paul Sabatier, Toulouse III, Toulouse F-31000, France.

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.

KEYWORDS:

4-Hydroxytamoxifen; Endoxifen; Tamoxifen; Tamoxifen-N-oxide; UPLC–MS/MS

PMID:
25173109
DOI:
10.1016/j.jpba.2014.07.033
[Indexed for MEDLINE]

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