pH-dependent degradation of nitrosocimetidine and its mechanisms

The degradation of nitrosocimetidine (NC) and its mechanism were found to be strongly dependent upon pH by monitoring NC and its degradation products by high-performance liquid chromatography (HPLC). NC was relatively stable at neutral pH, but it degraded rapidly under both acidic and alkaline conditions. In a strongly acidic solution, the degradation was shown to be entirely by denitrosation, but under alkaline conditions scarcely any denitrosation was observed and various other degradation products were found. At neutral pH, both these degradation mechanisms were observed. In neutral solution, the presence of thiol compounds greatly shortened the half life of NC, and enhanced its denitrosation. The high degradation rate in acidic solution, the strong influence of thiol groups, and the preference of denitrosation at pH 0.3-5 can explain the discrepancy between the in vitro genotoxicity and the lack of carcinogenicity of NC.