Development and characterization of surfactant aggregates as pseudostationary phases in electrokinetic chromatography

Abstract

Electrokinetic chromatography (EKC) is a mode of capillary electrophoresis based on the partitioning of solutes between a second retentive phase and the run buffer. The second retentive phase, known as a pseudostationary phase, can be comprised of an array of materials including: micelles, vesicles, microemulsions, cyclodextrins, crown ethers and polymers. Due to the variety of possible additives as well as the versatility of the technique, EKC has been used for a wide variety of applications in the pharmaceutical, environmental and food industries. In this investigation, various surfactant aggregates were developed and characterized for use as novel pseudostationary phases in electrokinetic chromatography.In Chapter 2, the chiral surfactant dodecoxycarbonylvaline (DDCV) was incorporated as a mixed micelle, vesicle and microemulsion for the rapid separation of enantiomeric pharmaceutical drugs.Chapter 3 involved the development and characterization of four surfactant vesicle systems for use as pseudostationary phases in electrokinetic chromatography. Vesicles are large aggregates of monomers consisting of one (unilamellar) or more (multilamellar) concentric spherical bilayers surrounding one or more internal cavities of solvent. These investigated vesicle systems demonstrated higher efficiencies, greater shape selectivity, larger elution window, and an alternative hydrophobic-hydrophilic selectivity compared to conventional micellar pseudostationary phases.xviThrough linear solvation energy relationship analysis, it was determined that the cohesiveness and hydrogen bond acidity of the retentive phase had the greatest impact on the observed retention and selectivity.As a result of the bilayer structure of vesicles, very similar to that of biological membranes, Chapter 4 presents the use of vesicle electrokinetic chromatography (VEKC) as an in-direct estimator for the intestinal permeability of drug candidates. In this study, retention factor (partitioning) in VEKC was correlated to octanol-water partition coefficients, cell monolayer permeability and plasma levels for a large number of pharmaceutical drug candidates. Retention factor in VEKC showed a statistically significant correlation to these in-vitro and in-vivo permeability assays.Chapter 5 presents an investigation of retention and selectivity utilizing the CTAB/SOS vesicle system in the presence of class I and II organic modifiers. Through inclusion of both classes of additive, alterations in electrophoretic (EOF, electrophoretic mobility of the vesicle) and chromatographic (retention, selectivity, elution range) parameters were observed.Appendix A presents the investigation of the reduction in matrix related signal suppression effects in electrospray ionization mass spectrometry (ESI-MS) using on-line two-dimensional liquid chromatography. A method incorporating on-line two-dimensional liquid chromatography mass spectrometry (LCLC-MS) was developed to compensate for matrix effects and signal suppression in qualitative and quantitative analysis.%%%%Ph.D.,…