title: Enantiomeric impurity determination in capillary electrophoresis using a highly-sulfated cyclodextrins-based method.
abstract: Capillary electrophoresis (CE), using highly-sulfated cyclodextrins as chiral selectors, has been applied to determine the chiral purity of pharmaceutical compounds. A chiral separation strategy, developed earlier for racaemic mixtures, was applied on four basic drugs (propranolol, atenolol, chlorpheniramine and tryptophan methylester). The aim was to develop validated separation methods which allow determination of 0.1% impurity levels of the unwanted enantiomers (distomer) in the presence of 99.9% of the active compound (eutomer). The linearity, quantification limits for the trace enantiomers and the precision of the measurements were determined. In a second part, impurity separations have been simulated in order to evaluate the required resolution when assaying impurities. It is shown that a baseline resolution of 1.5, generally accepted for racaemic mixtures, does not always allow good impurity determinations. Two alternative methods to solve this problem have been proposed.
authors.affiliation: Department of Analytical Chemistry and Pharmaceutical Technology, Pharmaceutical Institute, Vrije Universiteit Brussel, VUB, Laarbeeklaan 103, B-1090 Brussels, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Matthijs
authors.forename: Yvan
authors.initials: Y
authors.lastname: Vander Heyden
mesh_terms: D001262:Atenolol / Q000302:isolation & purification*; D002744:Chlorpheniramine / Q000302:isolation & purification*; D003198:Computer Simulation; D003505:Cyclodextrins / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D011433:Propranolol / Q000302:isolation & purification*; D015203:Reproducibility of Results; D013237:Stereoisomerism; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000302:isolation & purification
chemical_list: D003505:Cyclodextrins; D002744:Chlorpheniramine; D001262:Atenolol; C028129:tryptophan methyl ester; D014364:Tryptophan; D011433:Propranolol