Interaction of 5-aminosalicylic acid with nitrous acid: formation of the diazonium derivative and nitric oxide release

The reaction of 5-aminosalicylic acid (5-ASA) with nitrous acid has been studied at low pH under conditions that simulate a gastric environment. The course of the reaction was followed by UV-visible and fluorescence spectroscopy and the products were analyzed by high performance liquid chromatography (HPLC) with UV-visible and mass spectroscopic detectors. In addition, the formation of nitric oxide (NO) was estimated electrochemically. 5-ASA was readily consumed in a process catalyzed by chloride and thiocyanate, whose rate is first order in 5-ASA and second order in nitrous acid. 2-Hydroxy-5-diazonium benzoic acid (diazonium derivative) and NO were detected as products of the reaction. From the NO formation profiles, it is concluded that NO is produced as a minor product in a process parallel to the path that leads to generation of the diazonium derivative. While the formation of NO could be beneficial for the protection of the stomach, the generation of the diazonium derivative could be considered a potentially toxic process. Key words: 5-aminosalicylic acid, mesalazine, nitrous acid, nitrite, diazonium derivative, nitric oxide. On a etudie la reaction de l'acide 5-aminosalicylique (5-AAS) avec l'acide nitreux, a un pH faible, dans des conditions qui simulent un environnement gastrique. On a suivi l'evolution de la reaction par spectroscopies UV-visible et de fluorescence et on a analyse les produits par chromatographie liquide a haute performance (CLHP) avec des detecteurs par spectroscopie UV-visible et de masse. De plus, on a fait appel a une methode electrochimique pour evaluer la formation d'oxyde nitrique (NO). L'acide 5-aminosalicylique est rapidement consomme dans un processus catalyse par les ions chlorure et thiocyanate et pour lequel la vitesse est du premier ordre en 5-AAS et du second ordre en acide nitreux. On a detecte de l'acide 2-hydroxy-5-diazoniumbenzoique (derive diazonium) et du NO comme produis de la reaction. D'apres les profils de formation du NO, on en conclut que le NO se forme comme produit mineur dans un processus parallele a la voie qui conduit a la formation du derive diazonium. Alors que la formation du NO pourrait etre benefique pour la protection de l'estomac, la formation du derive diazonium peut etre consideree comme un processus potentiellement toxique. Mots-cles : acide 5-aminosalicylique, mesalazine, acide nitreux, nitrite, derive diazonium, oxyde nitrique.
Introduction Chronic inflammatory bowel pathologies such as ulcerative colitis and Crohn's disease cause inflammatory changes and ulcers of different types in the gastrointestinal mucosa. (1) 5-Aminosalicylic acid (5-ASA), the active [...]