An in vitro investigation of the complex system of acid catalyzed conversions of some proton pump inhibitors (PPI) have been carried out using differential pulse polarographhy (DPP) at the static mercury drop electrode (SMDE). Reactions were investigated in solutions buffered to pH values 2.0-8.0. The employed technique facilitated fast and timely monitoring of each PPI, in addition to its electroactive degradation products. Unlike previous techniques, which employed HPLC and UV spectroscopy, alone, or in combination, DPP facilitated fast and simultaneous recordings of all analytes in situ. This resulted in well-defined current-time profiles of individual electroactive degradation products, in addition to those of the starting materials. The results demonstrated that the rates of degradation of the investigated PPIs can be arranged in the following order: lansoprazole>omeprazole>pantoprazole. Furthermore, the rate of degradation of PPIs decreased with decreasing basicity of the corresponding benzimidazole nitrogen of PPIs, as predicted by the effect of individual substituents on each of the benzimidazole rings. The present study demonstrated that lansoprazole may have the fastest accumulation rate in the parietal cells, in addition to demonstrating the highest rate of conversion into the active inhibitor. At pH 6, however, pantoprazole was found to be the most stable, whereas lansoprazole and omeprazole underwent significant acid catalyzed decomposition. The cyclic sulfenamide of pantoprazole demonstrated highest stability among the three PPIs. Omeprazole, however, fell in the middle in terms of its stability and the stability of its corresponding cyclic sulfenamide. The present study may provide an insight for designing more potent new proton pump inhibitors.