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Dissertation
Electrokinetic chromatography using novel unilamellar vesicles for unique separations and prediction of intestinal permeability
Doctor of Philosophy (Ph.D.), Drexel University
Dec 2007
DOI:
https://doi.org/10.17918/etd-2579
Abstract
Using synthetic unilamellar vesicles as the pseudostationary phase in electrokinetic chromatography has several advantages. These types of vesicles are easy to prepare, inexpensive, and are similar in structure to cell membranes. The research presented in Chapter 2 explores the effect of changing the counterion of the cationic surfactant component of the vesicles from bromide to chloride. In addition, the effect of adding acetonitrile and 2-amino-1-butanol is investigated for both types of vesicles. Linear free energy relationship (LFER) analysis is performed on the vesicles in order to quantify the intermolecular interactions that are responsible for retention. The results indicate that there are unique selectivity differences between using cetyltrimethylammonium bromide (CTAB)/sodium n-octyl sulfate (SOS) and cetyltrimethylammonium chloride (CTAC)/SOS vesicles. Chapter 3 investigates the potential of using a partially fluorinated vesicle by combining CTAB with sodium perfluorooctanoate (FC7). The goal was to identify vesicles with smaller mean diameters in order to increase the sensitivity of the analysis. In addition, the effect of the fluorinated surfactant on selectivity was determined along with LFER analysis in order to compare to the CTAB/SOS vesicles. The resulting CTAB/FC7 vesicles were smaller than the CTAB/SOS vesicles and the CTAC/SOS vesicles. The CTAB/FC7 vesicles, however, were difficult to work with in terms of their reproducibility and unstable baseline at short wavelengths. In Chapter 4 are presented the correlations of Caco-2 permeability and intestinal permeability with retention factor measured by CTAB/SOS vesicles and CTAC/SOS vesicles for 22 pharmaceutical compounds. The results were promising in terms of the neutral and cationic analytes. However, there was difficulty in correlating the retention factors of the anionic compounds to both the Caco-2 and the intestinal permeabilities due to problems in being able to accurately calculate retention factor. In addition, the logarithm of the octanol-water partition coefficient for each compound was also correlated to the logarithm of the retention factors. This research has proven that two new unilamellar vesicle systems (CTAC/SOS and CTAB/FC7) are viable as pseudostationary phases for use in electrokinetic chromatography. Furthermore, there were promising results in terms advancing VEKC as a high throughput method for screening intestinal permeability.
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Details
- Title
- Electrokinetic chromatography using novel unilamellar vesicles for unique separations and prediction of intestinal permeability
- Creators
- Stephanie Ann Schuster - DU
- Contributors
- Joe Preston Foley (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Arts and Sciences; Chemistry; Drexel University
- Other Identifier
- 2579; 991014632619304721