| Summary: | 碩士 === 台北醫學院 === 藥學研究所 === 90 === Abstract
Tolmetin (TLM) and Zomepirac (Z) are used as photosensitizing nonsteroidal antiinflammatory drugs (NSAIDs). When TLM and Z were irradiated by a Hanovia 200W high pressure mercury lamp in methanol, a total of 8 photoproducts of TLM; TLM-1 to TLM-8 and 4 photoproducts of Z; Z-1 to Z-4 photoproducts were observed, respectively. Using preparative HPLC, photoproducts were isolated and their chemical structures were elucidated by UV、IR、MS、NMR and LC-MS spectroscopies.
Next, a rapid, sensitive, and accurate stability-indicating high perfor- mance liquid chromatographic assay method for determining the degra- dation of TLM and Z was developed and vali- dated under acidic, basic, or photo-irradiated conditions. The quantitation was monitored with an Inertsil ODS-3V column using a mobile phase of methanol- 0.3%acetic acid = 64:36 (v/v) for TLM and acetonitrile- methanol - 0.3%acetic = 2:64:34(v/v) for Z detector set at 254nm. The related satistics of the developed methods including the system criteria, peak integrity, and resolution among the parent drug and its degradation products were calculated. The C.V.(%) of intraday and interday tests were lower than 2.3% and 4% , respectively. The percent recovery were between 97.14% ~ 101.73 %. Our established HPLC assay method shows good selectivity and specificity which is suitable for the stability measurement of TLM and Z.
The rates of photodegradation between TLM and Z present significant difference, no mater the solvent is MeOH or 20% MeOH/H2O. When proceeding first order graphical analysis of these two compounds, we find that k of TLM is almost ten folds to B. After that, we use TLM, which possess more sensitive property to UV light. With different concentrations, alcohol solvents, and concentrations of 20% MeOH/H2O, to look forward to find out the exact photokinetic model of TLM. In our experimental model, the kinetic of TLM of high concentration is zero order. As for the results of using three alcoholic solvents, they showed an inverse proportional relationship between kinetics and dielectric constant of TLM. Hence we supposed that photokinetics of TLM might go through free radical reaction instead of ionic reaction.
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