title: 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.
abstract: 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. The three methods make it possible to obtain excellent enantioseparations (R(s) >3) with analysis times lower than 15 min, and the calculated limits of detection allow for the determination of minor enantiomeric impurities (0.1%). Enantiomeric purity obtained for dextrorotatory and levorotatory enantiomers was superior to 99.9% and equal to 98.9%, respectively, which proved the success of the semipreparative enantioseparation. A brief comparison of the performances of the analytical methods completes this work.
authors.affiliation: Laboratoire de Chimie Analytique EA 4034, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Lille 2, BP 83, 3 rue du Pr. Laguesse, 59006 Lille Cedex, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Danel
authors.forename: Christine
authors.initials: C
authors.lastname: Barthélémy
authors.forename: Dalila
authors.initials: D
authors.lastname: Azarzar
authors.forename: Hugues
authors.initials: H
authors.lastname: Robert
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bonte
authors.forename: Pascal
authors.initials: P
authors.lastname: Odou
authors.forename: Claude
authors.initials: C
authors.lastname: Vaccher
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D019075:Electrophoresis, Capillary / Q000379:methods*; D007555:Isoxazoles / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification; D015394:Molecular Structure; D000068882:Paliperidone Palmitate; D011743:Pyrimidines / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification; D015203:Reproducibility of Results; D018967:Risperidone / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification; D013237:Stereoisomerism
chemical_list: D007555:Isoxazoles; D011743:Pyrimidines; D018967:Risperidone; D000068882:Paliperidone Palmitate