Moore D E, Ghebremeskel K A, Chen B B, Wong E Y
School of Pharmacy, The University of Sydney, Australia.
Photochem Photobiol. 1998 Nov;68(5):685-91.
The nonsteroidal anti-inflammatory drugs (NSAID), naproxen, sulindac and indomethacin, were shown to donate electrons to nitro blue tetrazolium (NBT) when irradiated with UV light in deoxygenated aqueous buffer solution (pH 7.4, 30 degrees C). The reaction was monitored spectrophotometrically by the appearance of the diformazan reduction product from NBT. The electron transfer process facilitates the decomposition of the drugs. Naproxen in the presence of NBT is photodegraded principally to the alcohol (2-[1-hydroxyethyl]-6-methoxynaphthalene) at a rate approximately 20-fold faster than when irradiated alone in deoxygenated conditions. The photoproduct from naproxen also participates in the electron transfer to NBT but at a much slower rate than naproxen. Irradiation of sulindac or indomethacin in the presence of NBT caused the slow photoreduction of NBT to diformazan. In the absence of NBT, indomethacin and sulindac are essentially unreactive when irradiated in aqueous solution. The ability of a number of NSAID to act as electron donors in their ground state was studied by observing their oxidation by potassium peroxodisulfate in pH 7.0 phosphate buffer at 50 degrees C. The HPLC analysis of the drug remaining showed that the 2-arylpropionic acid NSAID (naproxen, ibuprofen, ketoprofen and suprofen) reacted at a rate equivalent to the thermal decomposition of peroxodisulfate. The major products were the same as detected in the photooxidation of these drugs, resulting from decarboxylation and oxygen addition but also included a dimeric compound. On the other hand, the NSAID that do not contain the propionic acid substituent all reacted more slowly with peroxodisulfate, enabling specific reaction rate constants to be evaluated.
非甾体抗炎药（NSAID）萘普生、舒林酸和吲哚美辛在pH 7.4、30℃的脱氧水性缓冲溶液中用紫外光照射时，被证明会向硝基蓝四唑（NBT）供电子。通过监测NBT的双甲臜还原产物的出现，用分光光度法对该反应进行监测。电子转移过程促进了药物的分解。在NBT存在下，萘普生主要光降解为醇（2-[1-羟乙基]-6-甲氧基萘），其降解速率比在脱氧条件下单独照射时快约20倍。萘普生的光产物也参与向NBT的电子转移，但速率比萘普生慢得多。在NBT存在下照射舒林酸或吲哚美辛会导致NBT缓慢光还原为双甲臜。在没有NBT的情况下，吲哚美辛和舒林酸在水溶液中照射时基本无反应。通过观察它们在50℃的pH 7.0磷酸盐缓冲液中被过二硫酸钾氧化的情况，研究了多种NSAID在基态下作为电子供体的能力。对剩余药物的HPLC分析表明，2-芳基丙酸类NSAID（萘普生、布洛芬、酮洛芬和舒洛芬）的反应速率与过二硫酸钾的热分解速率相当。主要产物与这些药物光氧化时检测到的产物相同，是由脱羧和加氧反应产生的，但也包括一种二聚体化合物。另一方面，不含丙酸取代基的NSAID与过二硫酸钾的反应都较慢，从而能够评估其具体的反应速率常数。
