Chiral characterization of deprenyl-N-oxide and other deprenyl metabolites by capillary electrophoresis using a dual cyclodextrin system in rat urine.
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)-beta-cyclodextrin (DIMEB) was suitable for the enantioresolution of deprenyl and its dealkylated derivatives, the enantiomers of deprenyl-N-oxide were just partly resolved. Carboxymethyl-beta-cyclodextrin (CMBCD) in as low as 2 mM concentration was capable of the enantiomer separation of all the nine examined compounds, however co-migration of 1R,2S-(-)-norephedrine and 1R,2R-(-)-pseudoephedrine, as well as 1S,2R-(+)-ephedrine and R-(-)-amphetamine was observed. This problem could be overcome by the use of a dual cyclodextrin system containing 4 mM DIMEB in addition to 2 mM 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.
Tábi
Tamás
T
Department of Pharmacodynamics, Semmelweis University, Nagyvárad tér 4., Budapest, H-1089 Hungary.
Magyar
Kálmán
K
Szöko
Eva
E
D000661:Amphetamine / Q000032:analysis / Q000302:isolation & purification; D000818:Animals; D001711:Biotransformation; D003505:Cyclodextrins; D019075:Electrophoresis, Capillary / Q000379:methods* / Q000592:standards; D004809:Ephedrine / Q000032:analysis / Q000302:isolation & purification; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism / Q000652:urine; D010665:Phenylpropanolamine / Q000032:analysis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012642:Selegiline / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine*; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
D003505:Cyclodextrins; D008996:Monoamine Oxidase Inhibitors; C484174:deprenyl-N-oxide; D012642:Selegiline; D010665:Phenylpropanolamine; D000661:Amphetamine; D004809:Ephedrine