Rapid on-line profiling of estrogen receptor binding metabolites of tamoxifen

Jeroen Kool; Rawi Ramautar; Sebastiaan M van Liempd; Joran Beckman; Frans J J de Kanter; John H N Meerman; Tim Schenk; Hubertus Irth; Jan N M Commandeur; Nico P E Vermeulen

doi:10.1021/jm0507936

Rapid on-line profiling of estrogen receptor binding metabolites of tamoxifen

J Med Chem. 2006 Jun 1;49(11):3287-92. doi: 10.1021/jm0507936.

Authors

Jeroen Kool¹, Rawi Ramautar, Sebastiaan M van Liempd, Joran Beckman, Frans J J de Kanter, John H N Meerman, Tim Schenk, Hubertus Irth, Jan N M Commandeur, Nico P E Vermeulen

Affiliation

¹ Leiden Amsterdam Center for Drug Research/Division of Molecular Toxicology, Department of Chemistry and Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.

PMID: 16722647
DOI: 10.1021/jm0507936

Abstract

Here we present a high-resolution screening (HRS) methodology for postcolumn on-line profiling of metabolites with affinity for the estrogen receptor alpha (ERalpha). Tamoxifen, which is metabolized into multiple metabolites, was used as the model compound. Most of the 14 metabolites detected exhibited affinity for the ERalpha. The HRS methodology shows great potential for metabolite bio-affinity profiling and application in drug discovery and development.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / metabolism*
Antineoplastic Agents / pharmacokinetics
Chromatography, High Pressure Liquid / instrumentation
Estrogen Antagonists / metabolism*
Estrogen Antagonists / pharmacokinetics
Estrogen Receptor alpha / metabolism*
In Vitro Techniques
Ligands
Microsomes, Liver / metabolism
Rats
Spectrometry, Mass, Electrospray Ionization
Swine
Tamoxifen / metabolism*
Tamoxifen / pharmacokinetics

Substances

Antineoplastic Agents
Estrogen Antagonists
Estrogen Receptor alpha
Ligands
Tamoxifen