Kinetic Analysis of the Effect of Polyhydric Alcohols on Ampicillin Degradation in the Presence and Absence of Aldehydes in Aqueous Solution

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Ampicillin degradation is accelerated by some carbohydrates. The kinetics of the degradation in the presence of polyhydric alcohols (xylitol, glycerin, ethyleneglycol) was studied in alkaline solution, because these alcohol were expected to exhibit a similar accelerating effect. In these experiments, the degradation of ampicillin obeyed apparent-first-order kinetics and the rate constrants increased with increasing concentration of polyhydric alcohols. The rate constant, however, was not affected by monohydric alcohols such as ethanol, propanol, and ethyleneglycol-monomethylether. The degradation of ampicillin was accelerated only by polyhydric alcohols which have adjacent hydroxy groups. This suggests that nucleophilic attack of a hydroxy anion on the β-lactam ring became easier as a result of simultaneous hydrogen bonding among the two adjacent hydroxy groups of alcohols and the amide-carbonyl and β-lactam carbonyl group of ampicillin. The rate accelerating effect of polyhydric alcohols on the degradation of ampicillin was depressed by the addition of aldehydes. This inhibition seems to be attributable to the steric hindrance and resonance effect of Schiff's base formation between the α-amino group of ampicillin and the aldehyde.
社団法人日本薬学会の論文
1985-12-25