Kinetics of acid degradation of proton pump inhibitors in the presence of a thiol

An in vitro investigation of the kinetics of the complex system of acid-catalyzed conversions and subsequent reactions of proton pump inhibitors (PPIs; omeprazole, lansoprazole and pantoprazole) was carried out using differential pulse polarography at the static mercury drop electrode. Reactions were investigated in the presence of 2-mercaptoethanol, in solutions buffered to pH values ranging from 2.0 to 5.0. The first-order reaction network was proposed for all conversions. The rate of degradation of PPIs and subsequent reactions with 2-mercaptoethanol were found to follow the following general order: lansoprazole > omeprazole > pantoprazole. The rate of conversion of PPIs into sulfenic acid was found to be directly dependent on the basicity of benzimidazole nitrogen of PPIs, which determines the electrophilic reactivity of the adjacent carbon (C2). The rate of conversion of the sulfenic acid of PPIs into the disulfide (the inhibition reaction) was found to be dependent on the electrophilicity of the sulfur atom of the sulfenic acid. © 2009 Wiley Periodicals, Inc. Int J Chem Kinet 41: 498–506, 2009