那普洛辛於有機溶媒中之光解研究
中文摘要
那普洛辛 ( Naproxen, NAP ) 為一非固醇類藥品，在臨床上用於治療風 濕性關節炎及痛風性關節炎，此類藥品具有光敏感性，當暴露於汞燈 或日光燈下不安定，在儲架期中若經光線照射，甚至有光毒性之顧慮，為了解其光化學反應途徑，本研究進行一系列之光分解相關實驗，
評估 NAP 之光安定性，以作為新劑型開發之參考。研究中將 NAP 置 於極性較高之甲醇溶媒中，當暴露於高壓汞燈下，會進行光解反應，
利用質譜儀、熔點測定儀、紫外線光譜儀、紅外線光譜儀、核磁共振 光譜儀進行光解產物結構的鑑定。
本研究發現 NAP 在高壓汞燈下，會進行光解反應，經鑑定確認結構 之產物有 3 個，主產物為 2-ethyl-6-methoxy-naphthalene, 1-(6-methoxy- naphthalen-2-yl)-ethanol 和 1-(6-methoxy-naphthalen-2-yl)-ethanone 。 有關濃度、溶媒、溫度等動力學光分解反應影響之研究方面，濃度效 應顯示為ㄧ階動力學模式。在溶媒效應方面發現，極性較大的溶媒對 那普洛辛光分解有增加的作用，且有成正相比的關係。在溫度效應方 面，依阿瑞尼士方程式可以計算出那普洛辛之活化能為 9.5 kcal/mol。
Studies of Photolysis of Naproxen in Organic Solvents
英文摘要
Naproxen (NAP), a well-known anti-inflammatory drug, is widely used for the treament of rhe umatoid and osteoarthritis in clinical therapy. However, it is light sensitive when exposed to m ercury lamp or sunlight. The drug is mostly unstable or even photoxic when stored on shelves under the exposure of hosehold light. In order to unveil the behavior of its photochemical path way, a systematic study of the photodegradation of Naproxen was undertaken. Furthermore, th e elucidation of the photosability characteristics of propionic acid-derived non-steroidal anti-in flammatory drugs is essential for the development of new dosage forms. In this study, Naprox en was placed in a polar solvent, such as methanol, while it exposed to high pressure mercury l amp, it undergoes photodegradation. The photodecomposition products were separated and id entified using UV, IR, MS and NMR spectroscopies.
When Naproxen was exposed to a high pressure mercury lamp, three new photodegradation pr oducts of NAP were observed and their structures identified. The main degraded products was 2-ethyl-6-methoxy-naphthalene, 1-(6-methoxy-naphthalen-2-yl)-ethanol and 1-(6-methoxy-na phthalen-2-yl)-ethanone. The influential factor with respect to molar concentration, solvent, te mperature and aerobic condition associated with the photodegradation were carefully investiga ted. The resultsof concentration effect showed that NAP fallows a pseudo first-order kinetic re action. At aerobic conditions, the photodegradation rate of Naproxen was accelerated. Accordi ng to the Arrhenius equation, the activation enrgy of NAP is found to be 9.5 kcal/mol.
