Controlled hydrolysis of ceftiofur sodium, a broad-spectrum cephalosporin; isolation and identification of hydrolysis products

Article abstract of DOI:10.1021/js950503g

Ceftiofur sodium is the salt of (6R,7R)-7-{[(2-amino-4-thiazoyl)-Z- (methoxyimino)acetyl]amino}-3-{[(2-furanylcarbonyl)thio]methyl}-8-oxo-5- thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid. This compound is very susceptible to acid, alkaline-, and enzyme-catalyzed hydrolysis, producing a number of unstable degradation products. In this report, we describe the preparation and identification of the hydrolysis products that are formed under controlled alkaline conditions. The primary hydrolysis product was desfuroyl ceftiofur, which is the most abundant metabolite in bovine blood. Desfuroyl ceftiofur was carefully oxidized with H₂O₂ to prepare the disulfide dimer, a urinary metabolite of ceftiotur sodium in the rat and cattle. Under acidic conditions, desfuroyl ceftiofur was converted to the corresponding thiolactone. The preparation of desacetyl cefotaxime, which is the oxygen analog of desfuroyl ceftiofur, is also described. Furoic acid was readily formed by hydrolytic cleavage of the thioester bond. Thiofuroic acid, formed by the less common cleavage on the alkyl side of the thioester bond, was also isolated.