Stereoselective metabolism of famprofazone in humans: N-dealkylation and β-and p-hydroxylation

✍ Scribed by Ho-Sang Shin

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 172 KB
• Volume: 9
• Category: Article
• ISSN: 0899-0042
• DOI: 10.1002/(sici)1520-636x(1997)9:1<52::aid-chir10>3.0.co;2-p

✦ Synopsis

Following administration of famprofazone to humans, the stereoselective metabolism from the drug to its known metabolites (+,-)-ephedrine, (+,-)pseudoephedrine, (+,-)-norephedrine, (+,-)-norpseudoephedrine, (+,-)-p-hydroxyamphetamine, (+,-)-p-hydroxymethamphetamine, and (+,-)-p-hydroxynorephedrine was studied. The enantiomers of the metabolites were derivatized with ␣-methoxy-␣-(trifluoromethyl)-phenylacetyl chloride (MTPA.Cl) as the chiral derivatizing agent for amino groups and N-methyl-N-trimethylsilyl trifluoroacetamide (MSTFA) or N-methyl-N-triethylsilyl trifluoroacetamide (MTESTFA) as protecting agents of the hydroxyl groups. The diastereomeric derivatives were well separated by capillary gas-liquid chromatography and determined by mass spectrometry with selected-ion monitoring (SIM). (-)-Methamphetamine, (-)-amphetamine, (-)-p-hydroxyamphetamine, and (-)-phydroxymethamphetamine were excreted in greater amounts than their enantiomers after administration of racemic famprofazone; and (-)-ephedrine, (-)-pseudoephedrine, (-)-norephedrine, and (-)-norpseudoephedrine were found in higher concentration than their enantiomers. Famprofazone was metabolized by product and substrate stereoselective N-dealkylation, ␤-hydroxylation, and p-hydroxylation, metabolites of which may be predominantly responsible for the side effects of famprofazone. Chirality 9: 52-58, 1997.