Slow, spontaneous degradation of lansoprazole, omeprazole and pantoprazole tablets: isolation and structural characterization of the toxic antioxidants 3H-benzimidazole-2-thiones

The spontaneous degradation of lansoprazole, omeprazole and pantoprazole tablets upon long-term and forced storage conditions was determined by high performance liquid chromatography (HPLC). The more abundant products could be isolated by liquid chromatography and their molecular weights determined by Mass Spectrometry (MS). Their structures, established according to their spectroscopic data, were compared to those of either the literature or of authentic samples. Thus lansoprazole led mainly to a mixture of 3H-benzimidazole-2-thione (2a) and 3H-benzimidazole-2-one (2c), omeprazole mainly to a mixture of 5-methoxy-3H-benzimidazole-2-thione (1a) and 2-hydroxymethyl-3, 5-dimethyl-4-methoxypyridine (1b), and pantoprazole, to 5-difluoromethoxy-3H-benzimidazole-2-thione (3a) and 2-hydroxymethyl-3, 4-dimethoxypyridine (3b). Although some of the degradation products had already been observed under different conditions, the detection of benzimidazole-2-thiones is unprecedented and their involvement as possible physiological, yet toxic antioxidants must be emphasized. Plausible, unified mechanisms for the formation of the different degradation products observed herein and in previous papers from the literature are suggested.