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

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

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.

Publication types

  • Validation Study

MeSH terms

  • Antineoplastic Agents, Hormonal / blood*
  • Antineoplastic Agents, Hormonal / pharmacokinetics
  • Breast Neoplasms / blood*
  • Breast Neoplasms / drug therapy
  • Calibration
  • Chromatography, Liquid / methods*
  • Chromatography, Liquid / standards
  • Drug Monitoring / methods*
  • Drug Monitoring / standards
  • Female
  • France
  • Humans
  • Metabolic Detoxication, Phase I
  • Reference Standards
  • Registries
  • Reproducibility of Results
  • Selective Estrogen Receptor Modulators / blood*
  • Selective Estrogen Receptor Modulators / pharmacokinetics
  • Spectrometry, Mass, Electrospray Ionization* / standards
  • Tamoxifen / analogs & derivatives
  • Tamoxifen / blood*
  • Tamoxifen / pharmacokinetics
  • Tandem Mass Spectrometry* / standards

Substances

  • Antineoplastic Agents, Hormonal
  • Selective Estrogen Receptor Modulators
  • Tamoxifen
  • afimoxifene
  • 4-hydroxy-N-desmethyltamoxifen
  • tamoxifen N-oxide
  • N-desmethyltamoxifen