title: Development and validation of a nonaqueous capillary electrophoretic method for the enantiomeric purity determination of a synthetic intermediate of new 3,4-dihydro-2,2-dimethyl-2H-1-benzopyrans using a single-isomer anionic cyclodextrin derivative and an ionic liquid.
abstract: The enantiomeric purity determination of a synthetic intermediate of new 3,4-dihydro-2,2-dimethyl-2H-1-benzopyrans, i.e. 4-amino-2,2-dimethyl-6-ethoxycarbonylamino-3,4-dihydro-2H-1-benzopyran, was successfully carried out using an anionic cyclodextrin (CD) derivative combined with a chiral ionic liquid (IL). In order to obtain high resolution and efficiency values, the addition of a chiral IL, i.e. ethylcholine bis(trifluoromethylsulfonyl)imide (EtChol NTf(2)), to the background electrolyte containing heptakis(2,3-di-O-methyl-6-O-sulfo)-β-CD (HDMS-β-CD) was found to be essential. A simultaneous increase in separation selectivity and enantioresolution seems to indicate a synergistic effect of HDMS-β-CD and EtChol NTf(2). The best enantioseparation of the key intermediate was achieved using a methanolic solution of 0.75M formic acid, 10mM ammonium formate, 1.5mM HDMS-β-CD and 5mM EtChol NTf(2). Levamisole was selected as internal standard. The optimized conditions allowed the determination of 0.1% of each enantiomer in the presence of its stereoisomer using the method of standard additions. The NACE method was then fully validated with respect to selectivity, response function, trueness, precision, accuracy, linearity and limits of detection and quantification.
authors.affiliation: Laboratory of Analytical Pharmaceutical Chemistry, Department of Pharmaceutical Sciences, CIRM, University of Liege, CHU, B36, B-4000 Liège, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Rousseau
authors.forename: Xavier
authors.initials: X
authors.lastname: Florence
authors.forename: Bernard
authors.initials: B
authors.lastname: Pirotte
authors.forename: Anne
authors.initials: A
authors.lastname: Varenne
authors.forename: Pierre
authors.initials: P
authors.lastname: Gareil
authors.forename: Didier
authors.initials: D
authors.lastname: Villemin
authors.forename: Patrice
authors.initials: P
authors.lastname: Chiap
authors.forename: Jacques
authors.initials: J
authors.lastname: Crommen
authors.forename: Marianne
authors.initials: M
authors.lastname: Fillet
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Servais
mesh_terms: D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000295:instrumentation / Q000379:methods*; D052578:Ionic Liquids / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D001578:Benzopyrans; D003505:Cyclodextrins; D052578:Ionic Liquids