title: Dynamic computer simulation of electrophoretic enantiomer migration order and separation in presence of a neutral cyclodextrin.
abstract: One-dimensional dynamic computer simulation was employed to investigate the separation and migration order change of ketoconazole enantiomers at low pH in presence of increasing amounts of (2-hydroxypropyl)-β-cyclodextrin (OHP-β-CD). The 1:1 interaction of ketoconazole with the neutral cyclodextrin was simulated under real experimental conditions and by varying input parameters for complex mobilities and complexation constants. Simulation results obtained with experimentally determined apparent ionic mobilities, complex mobilities, and complexation constants were found to compare well with the calculated separation selectivity and experimental data. Simulation data revealed that the migration order of the ketoconazole enantiomers at low (OHP-β-CD) concentrations (i.e. below migration order inversion) is essentially determined by the difference in complexation constants and at high (OHP-β-CD) concentrations (i.e. above migration order inversion) by the difference in complex mobilities. Furthermore, simulations with complex mobilities set to zero provided data that mimic migration order and separation with the chiral selector being immobilized. For the studied CEC configuration, no migration order inversion is predicted and separations are shown to be quicker and electrophoretic transport reduced in comparison to migration in free solution. The presented data illustrate that dynamic computer simulation is a valuable tool to study electrokinetic migration and separations of enantiomers in presence of a complexing agent.
authors.affiliation: Clinical Pharmacology Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Thormann
authors.forename: Lali
authors.initials: L
authors.lastname: Chankvetadze
authors.forename: Mehmet
authors.initials: M
authors.lastname: Gumustas
authors.forename: Bezhan
authors.initials: B
authors.lastname: Chankvetadze
mesh_terms: D003198:Computer Simulation; D003505:Cyclodextrins / Q000737:chemistry*; D004586:Electrophoresis / Q000379:methods*; D007654:Ketoconazole / Q000737:chemistry / Q000302:isolation & purification; D008956:Models, Chemical; D013237:Stereoisomerism
chemical_list: D003505:Cyclodextrins; D007654:Ketoconazole
keywords: Chiral separation; Enantiomer migration order; Simulation