Degradative behavior of a new bronchodilator, carbuterol, in aqueous solution

The degradation kinetics of carbuterol in aqueous solution were investigated at 85 degrees and constant ionic strength over the pH 0.25--13.3 range under anaerobic conditions. The results demonstrated a complex kinetic pattern involving specific acid and specific base catalyses at the pH extremes. Degradation resulted primarily from intramolecular catalysis and indicated that both the protonated and unprotonated phenolic groups participated in the reaction. High-pressure liquid chromatography was used to isolate carbuterol and its degradation product. Mass spectrometric examination showed that the degradation product was a cyclized derivative formed by intramolecular attack of the phenoxy group on the ureido carbonyl with ammonia expulsion. The apparent activation energy for carbuterol at pH 4.0 and 10.0 was 22.3 and 11.7 kcal/mole, respectively. The agreement between the calculated theoretical pH--rate profile and the experimental points supports the hypothesis presented concerning the reactions involved in carbuterol degradation.