Separation of reboxetine enantiomers by means of capillary electrophoresis.
The novel antidepressant reboxetine, a selective norepinephrine reuptake inhibitor, is increasingly used in the treatment of different forms of major depression. Reboxetine is a chiral compound, and is marketed as a racemic mixture of (R,R)- and (S,S)-reboxetine; however, the pharmacokinetic and toxicological profiles of the two enantiomers are rather different. For this reason, a simple capillary electrophoretic method for the separation of reboxetine enantiomers has been developed. Sulfobutyl ether-beta-cyclodextrin was chosen as the chiral selector, and several parameters, such as cyclodextrin and buffer concentration, buffer pH and capillary temperature were investigated in order to obtain good separation and acceptable run times. Using an uncoated, fused-silica capillary (internal diameter 50 microm, total length 48.5 cm, effective length 40.0 cm) and a background electrolyte consisting of a pH 3.0, 100 mM phosphate buffer containing 1.25 mM cyclodextrin, reboxetine enantiomers were baseline separated (resolution > 4) with a voltage of 20 kV in less than 16 min. Since pure enantiomers of reboxetine were not available, they were obtained from the racemic powder by means of direct-phase, high-performance liquid chromatography and their identity confirmed by circular dichroism spectra.
Department of Pharmaceutical Sciences, University of Bologna, Bologna, Italy.
Maria A
MA
Raggi
Roberto
R
Mandrioli
Cesare
C
Sabbioni
Carlo
C
Parenti
Giuseppe
G
Cannazza
Salvatore
S
Fanali
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000928:Antidepressive Agents / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003505:Cyclodextrins; D019075:Electrophoresis, Capillary / Q000379:methods; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry / Q000302:isolation & purification*; D000077593:Reboxetine; D012997:Solvents; D013696:Temperature; D047392:beta-Cyclodextrins
D000928:Antidepressive Agents; D003505:Cyclodextrins; D009025:Morpholines; D012997:Solvents; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C093196:SBE4-beta-cyclodextrin; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; D000077593:Reboxetine