Stereoselective metabolism of famprofazone in humans: N-dealkylation and ?-and p-hydroxylation
1997; Wiley; Volume: 9; Issue: 1 Linguagem: Inglês
10.1002/(sici)1520-636x(1997)9
ISSN1520-636X
Autores Tópico(s)Hormonal and reproductive studies
ResumoFollowing administration of famprofazone to humans, the stereoselective metabolism from the drug to its known metabolites (+,−)-ephedrine, (+,−)-pseudoephedrine, (+,−)-norephedrine, (+,−)-norpseudoephedrine, (+,−)-p-hydroxy-amphetamine, (+,−)-p-hydroxymethamphetamine, and (+,−)-p-hydroxynorephedrine was studied. The enantiomers of the metabolites were derivatized with α-methoxy-α-(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-(−)-hydroxymethamphetamine 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, β-hydroxylation, and p-hydroxylation, metabolites of which may be predominantly responsible for the side effects of famprofazone. Chirality 9:52–58, 1997. © 1997 Wiley-Liss, Inc.
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