那普洛辛於有機溶媒中之光解研究
Studies of Photolysis of Naproxen in Organic Solvents
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。 英文摘要Naproxen (NAP), a well-known anti-inflammatory drug, is widely used for the treament of rheumatoid and osteoarthritis in clinical therapy. However, it is light sensitive when exposed to mercury 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 pathway, a systematic study of the photodegradation of Naproxen was undertaken. Furthermore, the elucidation of the photosability characteristics of propionic acid-derived non-steroidal
anti-inflammatory drugs is essential for the development of new dosage forms. In this study, Naproxen was placed in a polar solvent, such as methanol, while it exposed to high pressure mercury lamp, it undergoes photodegradation. The photodecomposition products were separated and identified using UV, IR, MS and NMR spectroscopies. When Naproxen was exposed to a high pressure mercury lamp, three new
photodegradation products 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-naphthalen-2-yl)-ethanone. The influential factor with respect to molar concentration, solvent, temperature and aerobic condition associated with the photodegradation were carefully investigated. The resultsof concentration effect showed that NAP fallows a pseudo first-order
kinetic reaction. At aerobic conditions, the photodegradation rate of Naproxen was accelerated. According to the Arrhenius equation, the activation enrgy of NAP is found to be 9.5 kcal/mol.
