Capillary electrophoresis chiral separations: mathematical approach to determine optimum chiral selector concentration

C. LANCIONI, S. KEUNCHKARIAN Y L. GAGLIARDI

Praga

Congreso; 45th International Symposium on High Performance Liquid Phase Separations and Related Techniques; 2017

Cyclodextrins and their derivatives (CDs) are used in numerous commercial products, from several areas such as food, cosmetics or pharmaceuticals. CDs are cyclic oligosaccharides consisting of (α-1,4)-linked D-glucopyranose units, with a hydrophobic central cavity and a hydrophilic external surface. This properties make the CDs useful chemical tools: for increasing solubility of drugs, to improve drug delivery, for masking undesired tastes or smells, etc. All these features are related to its ability to include molecules inside the cavity. In analytical chemistry, researchers take advantage of its capacity to include molecules in the cavity but, furthermore, a relevant property is that CDs cavities expose chiral groups and, consequently, CDs use to act as chiral selectors. CDs are used in stationary phases, or also in the separation medium at different concentrations.The knowledge of the thermodynamic association constants between target compounds with different CDs is well appreciated. A general and systematic method to determine thermodynamic association constants between CDs and analytes would be a relevant and useful for all aforementioned fields. In this work we propose a rational method to determine thermodynamic association constants between ligands and analytes by capillary electrophoresis. We shed light over mathematical considerations and also over experimental aspects.In order to demonstrate how to apply in practice the procedure, 2-hydroxipropyl-β-CD was chosen as a model ligand, and four pharmaceutical drugs as model analytes: Pindolol, propranolol, oxprenolol and homatropine methylbromide, each of them under its two enantiomeric forms. Dissociation constants and electrophoretic mobilities of associated and free moiety are obtained, allowing to theoretically predict the dependencies of actual mobilities as a function of pC (pC= -log [CD]) in the whole range. Therefore, a multicriterion optimization function, T?, is composed to characterize/qualify with a single scalar function the electrophoretic separation of the eight compounds as a function of pC. Mathematical maximization of T' provides the optimum pC value. Finally, the experimental electrophoretic separation of all the 8 analytes at the optimum pC value are shown, and compared with other experimental separations at higher and lower concentrations.