A kinetic study on the degradation of erythromycin A in aqueous solution.
The pH is a critical factor determining the rate of the degradation of erythromycin A in aqueous solutions. However, the kinetics of the acid- and base-catalyzed degradation is still uncertain. This study used a sensitive coulometric detection method to determine concentrations of erythromycin A and its degradation products. To determine the buffer-independent rate constants, sodium acetate (0.05-0.2 M) and Tris-HCl (0.1-0.5 M) were used in a pH range of 3.5-5.5 and 7.0-9.0, respectively. In acidic conditions, anhydroerythromycin A appeared to be produced directly through an internal dehydration of erythromycin A-6,9-hemiketal which simultaneously established an equilibrium with erythromycin A enol ether on the other hand. In weakly alkaline conditions, hydroxide ion appeared to catalyze the hydrolysis of the lactonyl ester bond of erythromycin A-6,9-hemiketal by the pseudo-first-order kinetics, and the C13 --> C11 translactonization and internal dehydration reactions subsequently occurred to form pseudoerythromycin A enol ether. We suggest here a predictive model for reasonable interpretation of the kinetics of erythromycin A degradation in aqueous solutions, in which the observed rate constant was expressed by the sum of the partial reaction rate constants for the acid- and base-catalyzed degradation of erythromycin A-6,9-hemiketal as a function of pH in a range of 3.0-10.0.
Kim
Yong-Hak
YH
Division of Microbiology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Rd., Jefferson, AR 72079, USA.
Heinze
Thomas M
TM
Beger
Richard
R
Pothuluri
Jairaj V
JV
Cerniglia
Carl E
CE
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D004917:Erythromycin / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D012996:Solutions
D000900:Anti-Bacterial Agents; D002021:Buffers; D012996:Solutions; D004917:Erythromycin