Koshy K T, Cazers A R
Animal Health Drug Metabolism, The Upjohn Company, Kalamazoo, MI 49001, USA.
J Pharm Sci. 1997 Mar;86(3):389-95. doi: 10.1021/js950503g.
Ceftiofur sodium is the salt of (6R,7R)-7-{[(2-amino-4-thiazolyl)-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 ceftiofur 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.
头孢噻呋钠是(6R,7R)-7-{[(2-氨基-4-噻唑基)-Z-(甲氧基亚氨基)乙酰基]氨基}-3-{[(2-呋喃基羰基)硫代]甲基}-8-氧代-5-硫杂-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸的盐。该化合物极易受到酸、碱和酶催化水解，产生许多不稳定的降解产物。在本报告中，我们描述了在受控碱性条件下形成的水解产物的制备和鉴定。主要水解产物是去呋喃甲酰头孢噻呋，它是牛血液中含量最高的代谢物。用H2O2小心氧化去呋喃甲酰头孢噻呋以制备二硫键二聚体，它是头孢噻呋钠在大鼠和牛体内的尿液代谢物。在酸性条件下，去呋喃甲酰头孢噻呋转化为相应的硫内酯。还描述了去乙酰头孢噻肟的制备，它是去呋喃甲酰头孢噻呋的氧类似物。硫酯键的水解裂解很容易形成糠酸。硫酯键烷基侧较少见的裂解形成的硫代糠酸也被分离出来。
