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Stereoselective metabolism of famprofazone in humans: N‐dealkylation and β‐and p‐hydroxylation
Author(s) -
Shin HoSang
Publication year - 1997
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1997)9:1<52::aid-chir10>3.0.co;2-p
Subject(s) - chemistry , stereoselectivity , enantiomer , hydroxylation , ephedrine , pseudoephedrine , diastereomer , chromatography , trimethylsilyl , stereochemistry , organic chemistry , enzyme , pharmacology , medicine , catalysis
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.