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Chiral characterization of deprenyl‐ N ‐oxide and other deprenyl metabolites by capillary electrophoresis using a dual cyclodextrin system in rat urine
Author(s) -
Tábi Tamás,
Magyar Kálmán,
Szökő Éva
Publication year - 2003
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.200305468
Subject(s) - enantiomer , capillary electrophoresis , chemistry , cyclodextrin , chromatography , metabolite , ephedrine , stereospecificity , stereoselectivity , urine , biotransformation , selegiline , stereochemistry , enzyme , pharmacology , organic chemistry , biochemistry , medicine , disease , pathology , parkinson's disease , catalysis
A chiral capillary electrophoresis method has been developed for the simultaneous separation of the enantiomers of deprenyl and eight of its metabolites, among them the recently described metabolite deprenyl‐ N ‐oxide. Although heptakis‐(2,6‐di‐ O ‐methyl)‐β‐cyclodextrin (DIMEB) was suitable for the enantioresolution of deprenyl and its dealkylated derivatives, the enantiomers of deprenyl‐ N ‐oxide were just partly resolved. Carboxymethyl‐β‐cyclodextrin (CMBCD) in as low as 2 m M concentration was capable of the enantiomer separation of all the nine examined compounds, however co‐migration of 1 R ,2 S ‐(−)‐norephedrine and 1 R ,2 R ‐(−)‐pseudoephedrine, as well as 1 S ,2 R ‐(+)‐ephedrine and R ‐(−)‐amphetamine was observed. This problem could be overcome by the use of a dual cyclodextrin system containing 4 m M DIMEB in addition to 2 m M CMBCD; simultaneous separation of all the compounds could be achieved. The optimized method was used for the analysis of rat urine samples after 10 days of treatment of animals with either R ‐(−)‐ or S ‐(+)‐deprenyl. The stereospecific biotransformation of both deprenyl enantiomers was confirmed, and the stereoselectivity of N ‐oxide formation was demonstrated.