Influence of pH and temperature on kinetics of ceftiofur degradation in aqueous solutions

Citation
G. Sunkara et al., Influence of pH and temperature on kinetics of ceftiofur degradation in aqueous solutions, J PHARM PHA, 51(3), 1999, pp. 249-255
Citations number
13
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACY AND PHARMACOLOGY
ISSN journal
00223573 → ACNP
Volume
51
Issue
3
Year of publication
1999
Pages
249 - 255
Database
ISI
SICI code
0022-3573(199903)51:3<249:IOPATO>2.0.ZU;2-S
Abstract
The objective of this study was to evaluate the stability of ceftiofur (1 m g mL(-1)) in aqueous solutions at various pH (1, 3, 5, 7.4 and 10) and temp erature (0, 8, 25, 37 and 60 degrees C) conditions. The ionic strength of a ll these solutions was maintained at 0.5 M. Ceftiofur solutions at pH 5 and 7.4 and in distilled water (pH = 6.8) were tested at all the above tempera tures. All other solutions were tested at 60 degrees C. Over a period of 84 h, the stability was evaluated by quantifying ceftiofur and its degradatio n product, desfuroylceftiofur, in the incubation solutions. HPLC was used t o analyse these compounds. At 60 degrees C, the rate of degradation was significantly higher at pH 7.4 compared with pH 1, 3, 5 and distilled water. At both 60 degrees C and 25 degrees C, degradation in pH 10 buffer was rapid, with no detectable ceftio fur levels present at the end of 10 min incubation. Degradation rate consta nts of ceftiofur were 0.79+/-0.21, 0.61+/-0.03, 0.44+/-0.05, 1.27+/-0.04 an d 0.39+/-0.01 day(-1) at pH 1, 3, 5, 7.4 and in distilled water, respective ly. Formation of desfuroylceftiofur was the highest (65%) at pH 10. The rat e of degradation increased in all aqueous solutions with an increase in the incubation temperature. At pH 7.4 the degradation rate constants were 0.06 +/-0.01, 0.06+/-0.01, 0.65+/-0.17, and 1.27+/-0.05 day(-1) at 0, 8, 25, 37 and 67 degrees C, respectively. The energy of activation for ceftiofur degr adation was 25, 42 and 28 kcal mol(-1) at pH 5, 7.4 and in distilled water, respectively. Desfurylceftiofur formation was the greatest at alkaline pH compared with a cidic pH. Ceftiofur degradation accelerated the most at pH 7.4 and was most rapid at pH 10. The results of this study are consistent with rapid cleara nce of ceftiofur at physiological pH.