PIPERAZINEDIONE FORMATION FROM REACTION OF AMPICILLIN WITH CARBOHYDRATES AND ALCOHOLS IN AQUEOUS-SOLUTION

The accelerating effect of various carbohydrates (e.g. glucose and dextrans) and polyhydric alcoliols (e.g. sorbitol) on the rate of degradation of ampicillin in weakly alkaline solutions, has been shown to be due to a nucleophilic reaction mechanism involving formation of penicilloyl esters which subsequently undergo intramolecular aminolysis to yield a piperazine-2,5-dione derivative and, to a much smaller extent, hydrolysis to yield α-aminobenzylpenicilloic acid. Spectrophotometric and high-performance liquid Chromatographic methods have been developed for the determination of the piperazinedione compound and a facile procedure to obtain this new degradation product of ampicillin in large quantities is described. © 1979.