Separation of reboxetine enantiomers by means of capillary electrophoresis

Abstract

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.

Enantioselective determination of the novel antidepressant mirtazapine and its active demethylated metabolite in human plasma by means of capillary electrophoresis

“…Thus, the aim of this study is the development of a fast and feasible CE method for the enantioseparation of MRT and its active metabolite, and its application to human plasma samples for toxicological and therapeutic monitoring purposes. Due to its characteristics of high selectivity, efficiency and velocity, and the use of minute amounts of chiral selectors, CE is particularly suitable for the enantioseparation of chiral compounds [29][30][31][32][33][34]. The main disadvantage of CE is its limited sensitivity, which can, however, be compensated by a suitable pre-concentration of MRT and DMR present in the biological samples.…”

Enantioselective Synthesis of (+)-(S,S)-Reboxetine

“…4 However, (S,S)-reboxetine (1, Figure 1) is approximately 24 times more potent than the (R,R)-reboxetine (2), 5 and presents the best affinity and selectivity for norepinephrine transporter (NET). 6 So far, methods described in the literature to prepare reboxetine involve separation of reboxetine enantiomers by optical resolution, 7 capillary electrophoresis 8 or chiral HPLC, 9 synthesis via asymmetric Sharpless epoxidation, 10 and from (S)-2-(hydroxymethyl)morpholine as a chiral starting material. 11 Synthesis of arylthiomethyl morpholine analogues of reboxetine was also reported.…”

Spectrophotometric Determination of Reboxetine through Condensation and Diazo‐Coupling Reactions

“…A very few physicochemical methods were appeared in the literature for the assay of reboxetine methane sulphonate (REB) in biological fluids and pharmaceutical formulations. The methods so far reported include high-performance liquid chromatography (HPLC) 1-10 of different modes and detectors, capillary electrophoresis (CE) 11,12 , gas chromatography-mass spectroscopy (GC-MS) 13 and visible spectrophotometry 14 . The analytically important functional groups of REB were not properly exploited for designing suitable spectrophotometric methods for the determination REB.…”