KINETICS AND MECHANISM OF DEGRADATION OF AMPICILLIN IN SOLUTION

The kinetics of degradation of ampicillin (α‐aminobenzyl penicillin) in solution was investigated at 35° and constant ionic strength of 0.5 over a pH range of 0.8 to 10. The observed rates, obtained by measuring the remaining intact penicillin, were shown to observe first‐order kinetics and were shown to be significantly influenced by general acid and general base catalysis. The catalytic rate constants imposed by citrate and phosphate ions were calculated. In 0.08 N hydrochloric acid solution the apparent rate of reaction was shown to be accelerated with increasing neutral salt concentration and retarded due to the presence of alcohol. In a pH 4.94 buffer no primary salt effect was observed. The apparent heats of activation for ampicillin degradation in solution were determined to be 16.4, 18.3, and 9.2 kcal./mole, respectively, in buffers of pH 1.35, 4.93, and 9.78. The pH‐rate profile in buffer solutions showed a minimum at a pH of 4.85. However, at zero buffer concentration the maximum stability was shifted to a pH of 5.85. The agreement between the calculated theoretical curve and the experimental points (buffer‐free) supports the hypothesis presented concerning the reactions involved in the degradation of ampicillin in solution. Copyright © 1969 Wiley‐Liss, Inc., A Wiley Company