第一部分: 以液相層析質譜儀解析那普洛辛光解產物的化學構造 
第二部分: 那普洛辛與甘氨酸甲基酯光鍵結合之研究

中文摘要第一部分研究那普洛辛的光解產物。那普洛辛為一非類固醇類抗發炎藥物 (NSAIDs)，在臨床上具有解熱及鎮痛活性。然而，此藥暴露在汞燈或日光燈下具光敏感性，在架儲期中若經光線照射，甚至會具有光不安定性或光毒性的顧慮。因此，使用LC-ESI-MS的方法來解析那普洛辛的光解產物。那普洛辛以泛群光化學反應器 (裝置有16根8瓦低壓石英汞燈) 照射下，觀察到四種光解產物。光分解產物經由MS鑑定後分別確認為 1-(6-methoxy-naphthalen-2-yl)ethanol， 1-(6-methoxy- naphthalen -2-yl)-ethanone，2-(6-methoxy-naphthalen- 2-yl)propanoate 及 2-ethyl-6- methoxy-naphthalene。第二部分研究那普洛辛與氨基酸光鍵結合可能的形式及機轉。如果我們知道此機轉，應可以了解光過敏發生的原因。將那普洛辛及甘氨酸甲基酯的磷酸緩衝鹽溶液以低壓汞燈照射後，觀察到一個新的光反應後衍生的產物。它經由製備型層析法單離，並以LC-MS及GC-MS法鑑定此化合物為 N-[2-(6-Methoxy-2-naphthyl)- propanoyl]- glycine methyl ester。據此推測，那普洛辛與氨基酸間的光鍵結合是透過醯胺鍵連接而結合。

關鍵字

那普洛辛；光解產物；光鍵結合；液相層析質譜儀

並列摘要

Firstly, we focused on the studies of the photochemical decomposition products of naproxen. Naproxen is a typical non-steroidal anti-inflammatory drug (NSAID) which has analgesic and antipyretic activities. However, this drug is light sensitive when exposed to mercury lamps or sunlight. The drug is mostly unstable or even phototoxic when stored on shelves under the exposure of household light. By using the LC-ESI-MS method, we studied photochemical decomposition products of naproxen. When naproxen was exposed to a Panchum PR-2000 reactor, which equipped with 8W × 16 low-pressure quartz mercury lamps, four major major photoproducts were observed and separated. The main photodegraded products with their structures were confirmed by MS data. They were 1-(6-methoxy-naphthalen-2-yl)ethanol, 1-(6-methoxy- naphthalen -2-yl)-ethanone, 2-(6-methoxy-naphthalen-2-yl) propanoate and 2-ethyl-6- methoxy-naphthalene, respectively. Secondly, the photobinding behavior and possible mechanism between naproxen and amino acids was studied. If we know the mechanism, we may understand the cause of drug-induced photoallergy. Naproxen was coirradiated with glycine methyl ester in phosphate buffered saline (PBS) solution, with low-pressure quartz mercury lamps to observe any new photoproducts produced. One photobinding product, namely, N-[2-(6-Methoxy-2-naphthyl)- propanoyl]- glycine methyl ester, was isolated by the preparative liquid chromatographic method and the structure was identified by LC-MS and GC-MS. Based on this result, the possible photobinding mechanism between naproxen and amino acids is through an amide bond formation.

並列關鍵字

naproxen ； photoproducts ； photobinding ； LC-ESI-MS

參考文獻

Bosca F. and Miranda M.A. (1990) New photodegradation pathways for naproxen, a phototoxic nonsteroidal anti-inflammatory drug. Journal of Photochemistry and Photobiology A: Chemistry., 54: 131-134

Bosca F., Marin M.L. and Miranda M.A. (2001) Photoreactivity of non-steroidal anti-inflammatory 2-arylpropionic acids with photosensitizing side effects. Photochemistry and Photobiology. 74(5): 637-655

Castell J.V., Hernandez D., Gomez-Lechon M.J., Lahoz A., Miranda M.A., Morera I.M., Perez-Prieto J., and Serabia M. (1998) Photobinding of tiaprofenic acid and suprofen to proteins and cells: a combined study using radiolabeling , antibodies and laser flash photolysis of model bichromophores. Photochemistry and Photobiology., 68(5): 660-665

Dellagreca M. and Brigante M. (2004) Phototransformation and ecotoxicity of the drug naproxen-Na. Environ Chem Lett., 1: 237-241

De Vries H., Encinas S., Miranda M.A., Castell J.V., Beijersbergen an Henegouwen G.M. (1997) Photodegradation and photobinding of tiaprofenic acid: in vitro versus in vivo. Photochemistry and Photobiology, 66(4): 432-435

國際替代計量

第一部分: 以液相層析質譜儀解析那普洛辛光解產物的化學構造第二部分: 那普洛辛與甘氨酸甲基酯光鍵結合之研究

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