Capillary Electrophoresis Chiral Separations: Mathematical Approach to Determine Optimum Chiral Selector Concentration

CARLINA LANCIONI; SONIA KEUNCHKARIAN; LEONARDO G. GAGLIARDI

Praga

Simposio; 45th Symposium on High Performance Liquid Phase Separations and related Techniques (HPLC 2017); 2017

p { margin-bottom: 0.21cm; direction: ltr; color: rgb(0, 0, 0); line-height: 115%; }p.western { font-family: "Calibri",sans-serif; font-size: 11pt; }p.cjk { font-family: "SimSun","宋体"; font-size: 11pt; }p.ctl { font-family: "Times New Roman"; font-size: 11pt; }Cyclodextrinsand their derivatives (CDs)are used in numerous commercial products,from severalareas such as food, cosmetics or pharmaceuticals. CDs are cyclicoligosaccharides 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 increasingsolubility of drugs, to improve drug delivery, for masking undesiredtastes or smells, etc. etc.. All these features are related to itsability to include molecules inside the cavity. In analyticalchemistry, researchers take advantage of its capacity to includemolecules in the cavity but, furthermore, a relevant property is thatCDs cavities expose chiral groups and, consequently, CDs use to actas chiral selectors. CDs are used in stationary phases, or also inthe separation medium at different concentrations.Theknowledge of the thermodynamic association constants between targetcompounds with different CDs are well appreciated. A general andsystematic method to determine thermodynamic association constantsbetween CDs and analytes would be a relevant and useful for allaforementioned fields. Inthis work we propose a rational method to determine thermodynamicassociation constants between ligands and analytes by capillaryelectrophoresis. We shed light over mathematical considerations andalso over experimental aspects. In order to demonstrate Inorder to demonstrate how to apply in practice the procedure,2-hydroxipropyl-β-CD was chosen as a model ligand, and fourpharmaceutical drugs as model analytes: Pindolol, propranolol,oxprenolol and homatropine methylbromide, each of them under its twoenantiomeric forms. Dissociation constants and electrophoreticmobilities of associated and free moiety are obtained, allowing totheoretically predict the dependencies of actual mobilities as afunction of pC (pC= -log [CD]) in the whole range. Therefore, amulticriterion optimization function, T?, is composed tocharacterize/qualify with a single scalar function theelectrophoretic separation of the eight compounds as a function ofpC. Mathematical maximization of T´ provides the optimum pC value.Finally, theexperimental electrophoretic separation of all the 8 analytes at theoptimum pC value are shown, and compared with other experimentalseparations at concentrations higher and lower.