Critical parameters for the stability of cefquinome sulfate in aqueous solutions and solid phase

Abstract

Cefquinome sulfate is a veterinary, parenteral, fourth-generation cephalosporin with a methoxyimino–aminothiazolyl moiety into the acyl side chain and the quaternary quinoline group at position 3 of the cefem ring. Cefquinome sulfate is known to undergo degradation, which could be additionally increased by the presence of some critical factors such as temperature, relative air humidity, buffer components as well as hydrogen and hydroxide ions. The aim of this study was to evaluate the factors underlying the stability of cefquinome sulfate (CFQ) in aqueous solution and in the solid state taking into account general and specific acid–base hydrolysis in the pH range 0.45–10.48 at 343 K; the effect of temperature on the stability at 0% RH and an increased relative air humidity (RH = 76.4%); the influence of relative air humidity at 343 K (66.5–90%). To determine the observed rate constants, an isocratic HPLC–UV method was used. The three pKa values of cefquinome sulfate, kinetic (kobs., kpH), and activation parameters (Ea, ∆H≠, and ∆S≠) were determined.