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dc.contributor.authorJakubowski, Edward Michael, Jr.
dc.date.accessioned2013-04-08T18:06:02Z
dc.date.available2013-04-08T18:06:02Z
dc.date.issued1991
dc.identifier.urihttp://hdl.handle.net/10713/2580
dc.descriptionUniversity of Maryland, Baltimore. Biomedicinal Chemistry. Ph.D. 1991en_US
dc.description.abstractThe application of thermospray mass spectrometry to qualitative and quantitative chemical degradation studies was assessed. A cholinesterase reactivator drug, 2-pralidoxime (2-hydroxyiminomethyl-1-methylpyridinium chloride, 2-PAM), was elevated as a model compound. Extrapolation of the reported first order rate equations for 2-PAM degradation in solution to thermospray conditions predicted the percent breakdown that was observed in the thermospray system. Both apparent gas-phase and apparent solution-phase reactions were observed and the activation energies calculated from thermospray data were in close agreement with available literature values. Breakdown of 2-PAM was dependent on solution pH, temperature, and flow rate. This evidence supported a strong contribution from liquid-phase reactions. A thermal flow reactor, modeled after the thermospray probe, was developed. The reactor consisted of a directly heated, 30 cm long stainless steel tube (0.015 cm id) with a thermocouple to monitor temperature changes. The tube was electrically insulated from the rest of the liquid chromatography-mass spectrometry system by using non-conductive polymer HPLC tubing. Either a cation exchange column or a C{dollar}\sb{lcub}18{rcub}{dollar} column in series with the reactor was used to separate possible degradation products of 2-PAM. The characteristic conversion of 2-PAM to the corresponding 2-pyridone (in equilibrium with 2-hydroxy-1-methylpyridinium ion) was related to temperature and flow rate. Also shown was the incorporation of {dollar}\sp{lcub}18{rcub}{dollar}O-water into 2-pyridone as a function of reactor temperature. The {dollar}\sp{lcub}18{rcub}{dollar}O studies supported the accepted mechanism of 2-pyridone production from 2-PAM. Incorporation of {dollar}\sp{lcub}18{rcub}{dollar}O into fragments of other aldoximes was demonstrated under thermospray conditions. In general, the reactor demonstrated that solution-phase degradation can occur under simulated thermospray probe conditions. The reactor can also be used with a UV detector to analyze drug stability at elevated temperatures.en_US
dc.language.isoen_USen_US
dc.subjectChemistry, Analyticalen_US
dc.subjectChemistry, Pharmaceuticalen_US
dc.titleThe qualitative and quantitative assessment of aldoxime stability by thermospray mass spectrometryen_US
dc.typedissertationen_US
dc.contributor.advisorCallery, Patrick S.
dc.identifier.ispublishedYes
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