Studies on the phase I metabolism of the new designer drug 3-fluoromethcathinone using rabbit liver slices

Abstract

The metabolism of the novel designer drug 3-fluoromethcathinone (3-FMC), sold as "legal highs", was investigated in vitro via cryopreserved rabbit liver slices. The pharmacological properties and toxicological effects of 3-FMC and its metabolites are not known yet. It can be assumed that 3-FMC will cause effects similar to 4-methylmethcathinone (mephedrone) and methcathinone. For the metabolism studies, pretests were performed with rabbit liver slices incubated with kavain to evaluate optimal conditions. Finally, six known metabolites of kavain were revealed and therefore sufficient information about the suitability of the enzyme system of the rabbit liver slices was obtained. Under optimized conditions, 3-FMC was added to Krebs-Henseleit buffer, pH 7.4 containing NADPH and bicarbonate and incubated with a single rabbit liver slice at 37°C. The metabolism was monitored at 5, 30 and 180 min, respectively. The metabolites formed via the former cryopreserved rabbit liver slices were examined by LC/MS-TOF. Metabolites were identified by their exact masses and isotopic patterns. 3-Fluorocathinone, 3-fluorocathinone-imine, hydroxy-3-fluoromethcathinone and 3-fluoromethcathinone-diol were formed as the main metabolites.