title: Chiral separation of a basic drug with two chiral centers by electrokinetic chromatography for its pharmaceutical development.
abstract: A chiral method using capillary electrophoresis was developed for the separation of the four stereoisomers of a new chiral substance currently undergoing drug development as single enantiomer. After the selection of highly sulfated β-CD as chiral selector, an exhaustive study on the influence of several experimental variables on the resolution was performed, being the substitution degree of the CD a very decisive factor. Run time and resolutions were about 20min and higher than 2.0, respectively. The method was validated in terms of selectivity, linearity, accuracy, precision, and limits of detection and quantitation according to the requirements of the International Conference on Harmonisation for the determination of the chiral purity of a drug substance. The usefulness of the method was demonstrated in the control of stereoisomeric impurities in raw material as well as in the determination of the chiral stability of the drug in the solid state and in dosage forms used in safety assessment. Finally, the chiral method was used to investigate the possible in vivo inversion in biological samples.
authors: Department of Analytical Chemistry, Physical Chemistry and Chemical Engineering, Faculty of Biology, Environmental Sciences and Chemistry. Universidad de Alcalá, Ctra. Madrid-Barcelona Km. 33,600, 28871 Alcalá de Henares (Madrid), Spain.
authors: Ana Belén
authors: AB
authors: Martínez-Girón
authors: Department of Analytical Chemistry, Physical Chemistry and Chemical Engineering, Faculty of Biology, Environmental Sciences and Chemistry. Universidad de Alcalá, Ctra. Madrid-Barcelona Km. 33,600, 28871 Alcalá de Henares (Madrid), Spain.
authors: María Luisa
authors: ML
authors: Marina
authors: Department of Analytical Chemistry, Physical Chemistry and Chemical Engineering, Faculty of Biology, Environmental Sciences and Chemistry. Universidad de Alcalá, Ctra. Madrid-Barcelona Km. 33,600, 28871 Alcalá de Henares (Madrid), Spain. Electronic address: antonio.crego@uah.es.
authors: Antonio L
authors: AL
authors: Crego
mesh_terms: D020374:Chromatography, Micellar Electrokinetic Capillary; D004304:Dosage Forms; D007202:Indicators and Reagents; D057230:Limit of Detection; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000302:isolation & purification*; D015203:Reproducibility of Results; D013237:Stereoisomerism; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D004304:Dosage Forms; D007202:Indicators and Reagents; D004364:Pharmaceutical Preparations; D047392:beta-Cyclodextrins
keywords: Chiral drug; Chiral stability; Electrokinetic chromatography with cyclodextrins; Enantiomeric purity