DEGRADATION KINETICS AND ISOMERIZATION OF CEFDINIR, A NEW ORAL CEPHALOSPORIN, IN AQUEOUS-SOLUTION .2. HYDROLYTIC DEGRADATION PATHWAY AND MECHANISM FOR BETA-LACTAM RING-OPENED LACTONES

Hydrolysis of cefdinir leads to pH-dependent isomerizations and beta-l actam ring-opening. Lactam ring opened gamma-lactones were produced as a mixture of four diastereoisomers based on the lactone methyl, and C -6 isomerizations in acidic to neutral solutions. Cefdinir and as 7-ep imer were hydrolyzed to clarify the pathway leading to these lactones and the mechanism of C-6 epimerization with the aid of chiral separati on techniques. Chiral separation using a bovine serum albumin column w as employed to detect the beta-lactam ring opened products of cefdinir and its 7-epimer; the C-6 and C-7 isomerization was thereby observed; however, it was found to be pH-dependent at pH greater than or equal to 9. Optical activity detection applied to the lactones produced from cefdinir and its 7-epimer demonstrated that the corresponding peaks o f these lactones were enantiomeric pairs. In addition, the smallest ra te constant at pH 4 was observed for C-6 epimerization of the lactones , and it was found to proceed without deprotonation at C-6 by H-1-NMR spectroscopy. From the results of these studies, a plausible mechanism for C-6 epimerization has been proposed. Additionally, it was confirm ed that two degradation pathways were involved during hydrolysis of ce fdinir to the lactone.