Naproxen, photodegradation

Two case studies, naproxen and sulfamethoxazole, will be described briefly to illustrate how information concerning the excited state assists in elucidation of the mechanism of photodegradation. Their spectroscopic properties are detailed in Table 2.1, together with several other drugs given for comparative purposes. The state of ionization of the molecule can be a factor in the photochemistry, so it is relevant to show the information for neutral and anionic sulfamethoxazole (pKa 5.6). Ionization of naproxen (pKa 4.2) has no significant effect on its spectroscopic properties because the carboxyl group is distant from the naphthalene chromophore. 

Figure 2.12 Reaction mechanism for the photodegradation of naproxen in air-saturated aqueous solution pH 7.0. (From Moore, D.E. and Chappuis, P.P., Photochem. Photobiol., 47 173-181, 1988.)...

Significant results obtained in photodecarboxylation of 2-phenylpropionic acid have prompted a study of naproxen. The molecular mechanism of photosensitization of naproxen (2-[6-methoxy-2-naphthyl] propionic acid, 15) in red blood cells has been reported. In aqueous buffered solutions, photodegradation of naproxen leads to decarboxylated products with ethyl (16), 1-hydroxyethyl (17), and/or acetyl (18) side chains (Scheme 7, photodecarboxylation of naproxen). - When the methyl ester of naproxen complexed with LiY, NaY, and CsY zeolites is irradiated as hexane slurries under a nitrogen atmosphere for 6 h, no photoproducts are formed, and the methyl ester is photostable under the conditions employed, indicating that the zeohte environment also offers better protection to naproxen against the action of light. 

Bosca, R, Miranda, M. A., Vano, L., and Vargas, R, New photodegradation pathways for naproxen, a phototoxic non-steroidal anti-inflammatory drug, /. Photochem. Photobiol A Chem., 54, 131, 1990. 

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