ISSN:
0899-0042
Keywords:
famprofazone
;
stereoselective metabolism
;
N-dealkylation
;
β-hydroxylation
;
p-hydroxylation
;
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Following 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.
Additional Material:
5 Ill.
Type of Medium:
Electronic Resource
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