- 學位論文
氟白普洛芬於醇性溶媒之光解研究
Photolytic Studies of Flurbiprofen in Alcoholic Solvents
摘要
中文摘要 氟白普洛芬（FB）為一具有光敏感特性的非類固醇抗發炎藥物（NSAIDs）。為發展一敏感度高、準確的安定性指標之高壓液相層析分析法，並藉此來定量氟白普洛芬並觀察其光解反應。液相層析方法是使用Inertsil ODS-3V管柱，移動相組成為甲醇：氰甲烷：純水（加入1%醋酸）為2:4:4，UV檢測器波長設定在247nm。進而將氟白普洛芬檢量線作線性回歸、日內及日間精密度（Precision）試驗並予以確效。檢量線的R2值為0.9984，而日內、日間試驗的C.V.(%)值皆低於2.5% 和3.2%，模擬回收率亦在99.35%~101.61%之間。以上結果顯示，已發展出的HPLC分析方法具有良好的選擇性和專一性。 當將氟白普洛芬之甲醇溶液以Philips 400-W紫外燈照射，可觀察到氟白普洛芬有醇基（FB-1）、酮基（FB-2）及酯類（FB-3）三種光解衍生產物的產生。而當於乙醇溶液，酸性條件下，亦可觀察到氟白普洛芬乙基酯（FB-4）的生成。這些光解產物除以製備型高壓液相層析系統逐一單離，之後並藉由EI-MS、UV、IR、1H-,13C-NMR之檢測來解析其化學結構。 以不同濃度、不同溶媒的兩項變異，來觀察氟白普洛芬之光解動力學情形。結果發現，氟白普洛芬於高濃度對進行光分解會呈現零階次動力學模式，低濃度則較偏向一階次動力學模式；藉由使用不同醇類溶媒作仔細的觀察，則可看到其動力學模式，隨著溶媒極性的降低，而較偏向一階次動力學模式。
並列摘要
Abstract Flurbiprofen (FB) is one of photosensitizing non-steroidal anti-inflammatory drugs (NSAIDs). A sensitive, and accurate stability-indicating high performance liquid chromatography for determining the photodegradation of FB was developed and validated with linear regression of calibration curve, intra-day test, inter-day test. The quantitation for FB was monitored with an Inertsil ODS-3V column. The component of mobile phase was methanol- acetonitrile -deionized water (with 1% acetic acid added) = 2:4:4 and setting of UV detector was 247 nm. The R square of calibration curve regression was 0.9984 and the C.V. (%) of intra-day and inter-day tests was lower than 2.5% and 3.2%, respectively. The mimic percent recovery were between 99.35%~101.61%. The above results showed that our established HPLC assay method exhibit good selectivity and specificity. When FB was irradiated with a Philips 400-W UV lamp in methanol, 3 photoproducts of FB; ketone (FB-1), aldehyde (FB-2) and methyl ester (FB-3) could be observed, respectively. FB-ethyl ester (FB-4) also could be observed, when FB was dissolved in ethanol in acidic condition. Using preparative HPLC system, the resulting photoproducts were isolated and their chemical structures were analyzed by EI-MS、UV、IR、1H-,13C-NMR spectroscopies. Under the conditions of different concentrations and various alcoholic solvents, the photo-kinetic behaviors of FB were observed. The kinetics of FB under the photo-irradiation conditions followed the first order at lower concentrations. The kinetic results of FB followed the first order in n-propanol and zeroth order in methanol solutions.