ISOLATION AND STRUCTURE ELUCIDATION OF THE MAJOR DEGRADATION PRODUCTSOF CEFACLOR FORMED UNDER AQUEOUS ACIDIC CONDITIONS

The aqueous acidic degradation of the oral cephalosporin cefaclor was investigated. A number of degradation products were isolated and chara cterized. The degradation products can be loosely classified into thre e categories: thiazole derivatives, pyrazine derivatives, and simple h ydrolysis or rearrangement products. Degradation pathways are proposed that involve (1) hydrolysis of the beta-lactam carbonyl with subseque nt rearrangement, (2) ring contraction of the six-membered cephem nucl eus to five-membered thiazole derivatives through an episulfonium ion intermediate, and (3) attack of the primary amine of the phenylglycyl side chain on the ''masked aldehyde'' at carbon-6 to form fluorescent substituted pyrazines.