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.