title: 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.
abstract: Hydrolysis of cefdinir leads to pH-dependent isomerizations and beta-lactam 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 its 7-epimer were hydrolyzed to clarify the pathway leading to these lactones and the mechanism of C-6 epimerization with the aid of chiral separation techniques. Chiral separation using a bovine serum albumin column was 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 > or = 9. Optical activity detection applied to the lactones produced from cefdinir and its 7-epimer demonstrated that the corresponding peaks of these lactones were enantiomeric pairs. In addition, the smallest rate 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 1H-NMR spectroscopy. From the results of these studies, a plausible mechanism for C-6 epimerization has been proposed. Additionally, it was confirmed that two degradation pathways were involved during hydrolysis of cefdinir to the lactone.
authors.affiliation: Quality Assurance Laboratory, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okamoto
authors.forename: K
authors.initials: K
authors.lastname: Kiriyama
authors.forename: Y
authors.initials: Y
authors.lastname: Namiki
authors.forename: J
authors.initials: J
authors.lastname: Matsushita
authors.forename: M
authors.initials: M
authors.lastname: Fujioka
authors.forename: T
authors.initials: T
authors.lastname: Yasuda
mesh_terms: D000284:Administration, Oral; D000077525:Cefdinir; D002511:Cephalosporins / Q000737:chemistry*; D006868:Hydrolysis; D012996:Solutions; D013237:Stereoisomerism
chemical_list: D002511:Cephalosporins; D012996:Solutions; D000077525:Cefdinir