Optimization and validation of an enantioselective method for a chiral drug with eight stereo‐isomers in capillary electrophoresis

Abstract

Highly selective capillary electrophoresis (CE) screening methods were applied to find a satisfactory separation of a chiral drug with eight stereoisomeric compounds. The initial separation conditions were further optimized using response surface modelling by applying a Box-Behnken experimental design. This approach resulted in a rapid and efficient optimization of the buffer concentration, the concentration of two cyclodextrins, and the run voltage, in order to obtain final separation conditions of the method. Further optimization and validation of the system in terms of sensitivity and robustness resulted in a method that is suitable for quality control release purposes.

Response surface examination of the relationship between experimental conditions and product distribution in electrophoretically mediated microanalysis

“…Fortunately, various chemometric multivariate techniques including experimental design and response surface methodology (RSM) have been devised to aid in optimizing the performance of a system, including studies on the optimization of CE methods [34][35][36][37][38][39][40][41][42]. In addition, we have recently shown the first incorporation of RSM in ACE to effectively predict the significance of experimental conditions on protein-ligand binding [43].…”

Chiral separation in capillary electrophoresis using dual neutral cyclodextrins: Theoretical models of electrophoretic mobility difference and separation selectivity

“…To date, it has not been possible to predict the right selector based on physicochemical properties and structural information of enantiomers [25][26][27][28]. The right type of CD has to be determined at different concentrations, various pH, and different buffer concentrations [5-8, 11-14, 25-28].…”

Capillary electrophoresis for the analysis of small‐molecule pharmaceuticals

“…CE has become the technique of choice for enantiomeric separations [47][48][49] in some companies. Several companies [46,[50][51][52][53][54] have published generic approaches for chiral method development. The importance of using orthogonal methods and techniques in method evaluation and validation has been stressed [46].…”

“…Several pharmaceutical companies [46,[49][50][51][52][53][54] have recently published generic approaches for chiral method development.…”