The kinetics of degradation of chloramphenicol in solution: I. A study of the rate of formation of chloride ion in aqueous media

Authors

  • T. Higuchi,

    1. School of Pharmacy, University of Wisconsin
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  • Charles D. Bias

    1. School of Pharmacy, University of Wisconsin
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    • This paper is based in part on a thesis submitted by C. D. Bias to the Graduate School of the University of Wisconsin in partial fulfillment of the requirements for the degree of Master of Science.


Abstract

A chemical kinetics study of the rate of formation of chloride ions in aqueous solutions of chloramphenicol at elevated temperatures has been made. The data obtained indicate that the over-all rate of chloride production is a summation of the rates of at least three first-order reactions: direct uncatalyzed hydrolytic cleavage of chlorine ions from whole chloramphenicol molecules, direct hydroxyl ion catalyzed cleavage of chloride ions from whole chloramphenicol molecules, and hydrolysis of chloramphenicol at the amide linkage, then subsequent hydrolysis of the dichloroacetate ions formed to yield chloride ions and other degradation products. The rates of the several reactions have been separated by mathematical analysis from each other in the over-all rate and the heats of activation have been determined. The results for the dichloroacetate reaction are in excellent agreement with those of Kunze. The present study is an example of how kinetic studies can be used to elucidate the mechanism of breakdown of complex drugs.

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