Analytical and semipreparative enantioseparation of 9-hydroxyrisperidone, the main metabolite of risperidone, using high-performance liquid chromatography and capillary electrophoresis. Validation and determination of enantiomeric purity.

The HPLC semipreparative enantioseparation of 9-hydroxyrisperidone (9-OHRisp) was studied by optimizing various experimental conditions: the nature of the chiral stationary phase (CSP), mobile phase composition, temperature and analyte loading. This semipreparative enantioseparation was successfully completed using the polysaccharide Chiralcel OJ chiral stationary phase and a n-hexane/ethanol/methanol (50/35/15, v/v/v) ternary mobile phase. To assess the enantiomeric purity of both isolated isomers, three analytical methods using UV detection were developed and validated: one CE method using dual cyclodextrin mode and two HPLC methods using either the Chiralcel OJ CSP in normal-phase mode or the alpha-acid glycoprotein (alpha-AGP) CSP in reversed-phase mode.

Enantioselective analysis of the antipsychotic 9-hydroxyrisperidone, main metabolite of risperidone, by chiral capillary EKC using dual CDs.

An analytical method for the enantioseparation of the 9-hydroxyrisperidone, main metabolite of the antipsychotic risperidone (Risp), was developed by CD-EKC in the dual CDs mode using anionic and neutral CDs at acidic pH 2.5. Preliminary experiments allowed us to select the more suitable couple of CDs composed of sulfated-alpha-CD and hydroxypropylated-beta-CD.