Investigation of free radical metabolism of raloxifene by NADPH-fortified human liver microsomes using liquid chromatography/ LTQ-Orbitrap

摘要

Previously, horseradish peroxidase was shown to metabolize raloxifene via a 1-electron oxidation to form a dimer presumably involving a free radical reaction (1). However, the formation of this raloxifene dimer has never been detected in liver microsomes from animal species or human in the presence of NADPH. We now report the identification and characterization of raloxifene dimers formed by NADPH-fortified human liver microsomes using high resolution accurate mass measurements and online hydrogen-deuterium exchange.