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dc.contributor.advisorLunte, Susan M
dc.contributor.authorCreamer, Jessica Stephens
dc.date.accessioned2017-01-08T18:34:37Z
dc.date.available2017-01-08T18:34:37Z
dc.date.issued2014-08-31
dc.date.submitted2014
dc.identifier.otherhttp://dissertations.umi.com/ku:13608
dc.identifier.urihttp://hdl.handle.net/1808/22513
dc.description.abstractMaintaining a consistent supply of pharmaceuticals to developing countries could save millions of lives per year. One of the major roadblocks in this effort is an abundance of substandard and counterfeit drugs in the supply chain. To prevent these products from being distributed, improved methodology and instrumentation for drug screening is needed. In these low-resource areas the availability of proper funding and laboratory space is limited. To replace the expensive liquid chromatography and mass spectrometry instrumentation traditionally used for quality control, capillary electrophoresis (CE) can be used. CE has a low startup cost and, because of the small sample and reagent volume requirements, the cost per test is kept to a minimum. Additionally, any methodology developed for CE can be transferred to the miniaturized platform of microchip electrophoresis (ME). ME further reduces the cost-per-test and provides the potential for a fully portable analytical device that can be used for on-site analysis. This method is particularly useful for screening pharmaceuticals throughout the many distribution lines, store houses, and clinics across a large country. In this dissertation, CE was used to develop methodology for the analysis of the peptide drug oxytocin (OT). OT is needed in developing countries to prevent death from post-partum hemorrhage. A major concern regarding the supply chain of peptide-based drugs is the degradation of these products when then are shipped and stored incorrectly. Several degradation products are produced when OT is subjected to heat-stress conditions. Deamidation, in particular, produces small molecular changes that have significant effects on the biological activity of the peptide. Initially, methodology for the separation and detection of desamino degradation products of OT was developed for CE-UV. OT contains three potential sites of deamidation, which leads to seven distinct desamino products. The separation was achieved following an optimization of the background electrolyte to include a pseudostationary phase and an organic modifier to increase selectivity and resolve the eight structurally similar peptides. To improve the functionality of the CE assay for OT integrity screening, the next step of was to further optimize the method for a separation of all of the known degradation products formed under heat-stressed OT formulations. However, current literature on the degradation of OT does not yet addressed the degradation of Pitocin pharmaceutical formulations that are prepared in water containing a small amount of acetic acid, to adjust the pH between 3-5, and 0.5% chlorobutanol as a preservative. To investigate the effect that CB and CB-like products have on the degradation of OT, LC-UV-MS was used to monitor the formation of degradation products as a function of time. The preliminary data shows that CB, and the structurally similar trichloroethanol (TCE), significantly stabilize OT from the heat-stress degradation. The addition of either of these trichloro species substantially reduces the rate of degradation observed over a 48 h period at 70 °C. Further work is needed on this project to determine the cause of this protective effect by performing structural studies of OT in the presence of CB or TCE. Finally, initial steps were taken towards the development of a low-cost portable ME device. A significant percentage of small molecule counterfeit drugs are formulated with the wrong amount of active ingredient. Current portable analytical methods available to monitor the pharmaceutical supply chain are limited in their quantitative abilities. By coupling ME to conductivity detection, it is possible to perform quantitative analysis of multiple species simultaneously. Initial experiments to evaluate system performance were performed using two first-line anti-tuberculosis drugs, ethambutol and isoniazid.
dc.format.extent165 pages
dc.language.isoen
dc.publisherUniversity of Kansas
dc.rightsCopyright held by the author.
dc.subjectAnalytical chemistry
dc.subjectBiotechnology
dc.subjectCapillary electrophoresis
dc.subjectDeveloping countries
dc.subjectMicrochip electrophoresis
dc.subjectPharmaceutical analysis
dc.subjectProtein therapeutic
dc.titleThe Development of Capillary and Microchip Electrophoresis Methods for the Analysis of Pharmaceuticals in Developing Countries
dc.typeDissertation
dc.contributor.cmtememberNordheden, Karen J
dc.contributor.cmtememberSiahaan, Teruna J
dc.contributor.cmtememberStobaugh, John F
dc.contributor.cmtememberWang, Micheal Z
dc.thesis.degreeDisciplinePharmaceutical Chemistry
dc.thesis.degreeLevelPh.D.
dc.identifier.orcidhttps://orcid.org/0000-0003-2890-4901
dc.rights.accessrightsopenAccess


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