Pharmaceutical analysis of the prodrug metronidazole benzoate
MetadataShow full item record
The dissertation includes two parts: analytical methodology applied in formulation development and clinical healthcare. The focus of the first part was pharmaceutical analysis during new formulation development for the prodrug metronidazole benzoate. In the second part, bioanalytical techniques (HPLC, CE, and LC-MS-MS) were applied in the monitoring of anti HIV drugs in combination therapies for HIV infection. |A brief background about the interdisciplinary application of analytical methodology was introduced. Antiretroviral drugs approved by the FDA and triple cocktail therapies were discussed as well as the prodrug metronidazole benzoate. |In Chapters 1 and 2, two new dosage forms, an oil-in-water emulsion and a lozenge, were developed. A sensitive, stability-indicating HPLC assay was also developed and validated for the stability, degradation and dissolution studies of the prodrug metronidazole benzoate in these formulations. Waters Millennium 32 PDA software and photodiode-array (PDA) detection were applied to determine the degradation products of metronidazole benzoate and their purity through library matching procedures and peak purity processing. |In Chapters 3 and 4, ion-pair chromatography (IPC) was applied to separate and quantitate the anti-HIV drugs zidovudine/lamivudine/nevirapine and zidovudine/ zalcitabine/nevirapine simultaneously in human plasma. Octane sulfonic acid sodium salt was chosen as the ion pair reagent. |In Chapters 5 and 6, gradient chromatography methods utilizing tandem mass spectrometry (LC-MS-MS) were developed and validated for the simultaneous measurement of the anti-HIV drugs lamivudine/stavudine /efavirenz and didanosine/stavudine/ritonavir in human serum. An ionization polarity switching technique was employed in the separation of lamivudine/stavudine /efavirenz. The effect of ion suppression from the matrix was studied. |In Chapters 7 and 8, capillary zone electrophoresis (CZE) was employed for the simultaneous determination of the anti-HIV drugs lamivudine/didanosine/saquinavir and lamivudine/didanosine/nevirapine in human serum. The effects of run buffer type, buffer concentration, and pH on the separation were investigated. |In Chapters 9 and 10, micellar electrokinetic chromatography (MEKC) methods were described in human serum for simultaneous determination of the anti-HIV drugs zidovudine/didanosine/nevirapine, zidovudine/didanosine/ritonavir, stavudine/ didanosine/saquinavir and stavudine/didanosine/efavirenz. Sodium dodecylsulfate (SDS) was used as the surfactant.