Characterization of in vitro metabolites from human liver microsomes using directly coupled hplc-nmr: application to a phenoxathiin monoamine oxidase-A inhibitor

Abstract

1. The metabolism of 1-ethylphenoxathiin-10,10-dioxide (BW1370U87), an experimental compound designed as an inhibitor of monoamine oxidase-A for use as a possible anti-depression agent, has been studied in a human liver microsome preparation.

2. The identities of the metabolites have been determined using directly coupled hplc-¹H nmr at 600 MHz in the stop-flow mode in this first study of in vitro xenobiotic metabolism using hplc-nmr.

3. The xenobiotic substances that were identified comprised the parent compound BW1370U87 (with -CH₂CH₃ at C1) together with sidechain-oxidized metabolites with C1 substituents of -CHOH.CH₃, -CH₂.CH₂OH, -CHOH.CH₂OH and -CH₂.COOH, plus the unsubstituted phenoxathiin-10,10-dioxide.