Oxidative degradation studies of an oxazolidinone-derived antibacterial agent, RWJ416457, in aqueous solutions

The rates of oxidative degradation of a new antibacterial drug, RWJ416457, in aqueous solutions were investigated over the pH-range of 2 to 10. Two oxidative degradates were identified and the influences of pH, buffer concentration, metal ions, metal chelating agents, and temperatures were studied. The pH, metal chelating agents, and metal ions significantly changed the product distribution in addition to the degradation rate. Oxidative degradation is believed to follow a hydrogen abstraction (HAT) pathway. One degradate was the major product under acidic conditions and its predominance is attributed to a resonance-stabilized intermediate. The importance of the resonance structure was diminished under neutral and basic conditions. The product distribution changed and two degradates were formed in equal amounts. The study results guided the formulation development to minimize oxidation.