Influence of pH, temperature, and buffers on the kinetics of ceftazidime degradation in aqueous solutions. 1995

M Zhou, and R E Notari
Department of Pharmaceutical Sciences, College of Pharmacy, Medical University of South Carolina, Charleston 29425, USA.

First-order rate constants (k) were determined for the hydrolysis of ceftazidime in the pH range of 0.5 to 8.5 at 45, 55, and 65 degrees C by a stability-indicating HPLC assay. In the absence of buffer effects, the pH-rate expression was k = kH1f1(aH+) + kH2f2(aH+) + kH3f3(aH+) + kSf3 + kOHf3(aOH-), where KH and KOH are the catalytic rate constants for the activity of hydrogen (aH+) and hydroxyl (aOH-) ions, respectively, and kS is the rate constant for spontaneous hydrolysis. The fractions of ceftazidime in various stages of dissociation (f1, f2, and f3) were calculated from kinetically determined apparent Ka values of 2.03 x 10(-2) and 4.85 x 10(-5). Catalytic constants (kcat) were calculated for formate, acetate, phosphate, and borate buffers, which accelerated hydrolysis. Each of the rate constants (kH1, kH2, kH3, kS, kOH, and kcat) were described as a function of temperature with calculated A and E values in the Arrhenius equation, kT = Ae-E/RT. Ceftazidime hydrolysis rate constants (k) were calculated as a function of pH, temperature, and buffer by combining the pH-rate expression with the buffer contributions calculated from kcat values and the temperature dependencies. These equations and their parameter values successfully calculated 95 of 104 experimentally determined rate constants with errors of < 10%. Maximum stability was observed in the relatively pH-independent region from 4.5 to 6.5. Hydrolysis rate constants at 30 degrees C were predicted and experimentally verified for four ceftazidime solutions, three of which (pH 4.4 acetate buffer and pH 5.5 and 6.5 phosphate buffers) maintained 90% of their initial concentration for approximately 1.5 days.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008433 Mathematics The deductive study of shape, quantity, and dependence. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Mathematic
D002021 Buffers A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. Buffer
D002442 Ceftazidime Semisynthetic, broad-spectrum antibacterial derived from CEPHALORIDINE and used especially for Pseudomonas and other gram-negative infections in debilitated patients. Ceftazidime Anhydrous,Ceftazidime Pentahydrate,Fortaz,Fortum,GR-20263,LY-139381,Pyridinium, 1-((7-(((2-amino-4-thiazolyl)((1-carboxy-1-methylethoxy)imino)acetyl)amino)-2-carboxy-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-en-3-yl)methyl)-, inner salt, pentahydrate, (6R-(6alpha,7beta(Z)))-,Tazidime,GR 20263,GR20263,LY 139381,LY139381
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D006868 Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water.
D013696 Temperature The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms. Temperatures

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