Degradation kinetics and mechanism of aminocephalosporins in aqueous solution: Cefadroxil

Akira Tsuji, Emi Nakashima, Yoshiharu Deguchi, Kazunori Nishide, Takayoshi Shimizu, Sumio Horiuchi, Kiyoyasu Ishikawa, Tsukinaka Yamana

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Abstract

The degradation kinetics and mechanism of a new, orally effective cephalosporin derivative, cefadroxil, in aqueous solution were investigated at pH 2.51‐11.5 at 35° and ionic strength 0.5. The degradation rates were determined by high‐pressure liquid chromatography. At constant pH and temperature, the degradation followed first‐order kinetics and a log k‐pH profile was presented. The shape of the rate‐pH profile resembled that for cephalexin or cephradine under the same conditions. Citrate and phosphate buffers enhanced general acid and base catalysis of the degradation. In aqueous solution, cefadroxil was shown to degrade by three parallel reactions: (a) intramolecular aminolysis by the C‐7 side‐chain amino group on the β‐lactam moiety, (b) water‐catalyzed or spontaneous hydrolysis, and (c) β‐lactam cleavage by the nucleophilic attack of hydroxide ion. In neutral and weak alkaline solutions, the main degradation products were two piperazine‐2,5‐diones and 3‐hydroxy‐4‐methyl‐2(5H)‐thiophenone, the former being formed from Reaction a, while the latter arose via the degradation pathways of Reactions b and/or c.

Original languageEnglish
Pages (from-to)1120-1128
Number of pages9
JournalJournal of Pharmaceutical Sciences
Volume70
Issue number10
DOIs
Publication statusPublished - 1981 Oct

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Keywords

  • Cefadroxil—degradation kinetics and mechanism, high‐pressure liquid chromatography, pH‐rate profile, intramolecular aminolysis to produce piperazinediones, buffer and temperature effects
  • Degradation kinetics—cefadroxil, high‐pressure liquid chromatography assay, pH‐rate profile, intramolecular aminolysis to produce piperazinediones, buffer and temperature effects a pH‐rate profile—cefadroxil, degradation kinetics and mechanism, intramolecular aminolysis to produce piperazinediones, buffer and temperature effects
  • Piperazinediones—cefadroxil degradation kinetics and mechanism, in‐tramolecular aminolysis

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Tsuji, A., Nakashima, E., Deguchi, Y., Nishide, K., Shimizu, T., Horiuchi, S., Ishikawa, K., & Yamana, T. (1981). Degradation kinetics and mechanism of aminocephalosporins in aqueous solution: Cefadroxil. Journal of Pharmaceutical Sciences, 70(10), 1120-1128. https://doi.org/10.1002/jps.2600701008