Development of a dual cyclodextrin system-capillary electrophoresis method for the determination of the enantiomeric purity of levosulpiride

In levosulpiride (L-SUL) pharmaceutical formulations, R-SUL should be considered as an enantiomeric impurity, and it is essential to have at disposal a rapid analytical method to control the chiral purity of the product. Quality by Design (QbD) [1] has been recently introduced into the pharmaceutical industry with the objective of achieving a desired state for pharmaceutical manufacturing and product quality [2]. In this study, for the first time in the literature, QbD was applied in the field of capillary electrophoresis (CE) chiral separations, in order to develop a rapid and reliable CE method suitable for the analysis of L-SUL and its chiral impurity. A dual cyclodextrin (CD) system made by sulfated-β-CD and methyl-β-CD was identified as the separation system leading to the best results in terms of selectivity. The effects of selected critical process parameters, both qualitative and quantitative, on enantioresolution and analysis time were deeply studied by a multivariate strategy involving a screening phase and response surface methodology. The application of QbD strategy made it possible to define a multivariate zone where the quality of analytical data was assured with a selected degree of probability.