Degradation Kinetics and Isomerization of Cefdinir, a New Oral Cephalosporin, in Aqueous Solution. 1

Abstract

0 Hydrolytic degradation products of cefdinir were studied in acidic (pH 1), neutral (pH 6), and basic (pH 9) solutions. Seven major degradation products were isolated by preparative and/or high-performance liquid chromatography and characterized by UV, IR, 1 H-NMR, and mass spectra. To clarify degradation pathways in each pH solution, kinetic and product analyses during hydrolysis of cefdinir were carried out along with the followup reaction of representative degradation products. Cefdinir was shown to degrade via two major degradation routes: -lactam ringopening and pH-dependent isomerizations (lactonization, epimerization at C-6 or C-7, syn−anti isomerization of N-oxime function).

Degradation Kinetics and Isomerization of Cefdinir, a New Oral Cephalosporin, in Aqueous Solution. 2. Hydrolytic Degradation Pathway and Mechanism for β-Lactam Ring Opened Lactones

“…Degradation Pathways To Yield 6 in Acidic to Neutral SolutionssBy the product and kinetic approach in the previous work, 3 it was clarified that cefdinir was hydrolyzed to afford 6 via two pathways, i.e., pathway 1, via product 1 in acidic to neutral solutions, and pathway 2, via the γ-lactone of cefdinir (5) in acidic solution.…”

“…Degradation kinetics and isomerization in the hydrolysis of cefdinir were investigated by product and kinetic analyses. As discussed in our previous work, 3 cefdinir is hydrolyzed via two major degradation routes, -lactam ring-opening and pH-dependent isomerizations. The -lactam ring opened lactones (6), obtained in the hydrolysis of cefdinir in acidic to neutral solutions, were characterized as a mixture of four diastereoisomers based on lactone methyl and C-6 epimerization by precise product analyses for the hydrolytic degradation products of cefdinir and its 7-epimer (3).…”

Isolation, structural elucidation and characterization of impurities in Cefdinir

“…NMR measurements were performed on a Bruker-Avance 300 MHz instrument (both for 1 H and 13 C) at 25 • C in DMSOd 6 . The 1 H NMR and 13 C chemical shift values were reported on the δ scale in ppm, relative to TMS (δ = 0.00) and DMSO-d 6 (δ = 39.5 ppm) as internal standard, respectively.…”

“…High performance liquid chromatographic (HPLC) methods have been reported in the literature [4,5] for the determination of Cefdinir using UV detection. Okamoto has carried out degradation kinetics and isomerization study of Cefdinir in aqueous solutions [6,7].…”

Synthesis of potential related compounds of Cefdinir

“…However, the degradation kinetics of cefdinir has been cited in the literature. 8 The preparation of these three contaminants has been necessary for the preparation of reference compounds for the quality control of bulk drugs and drug formulations, and pathways have been developed starting from the parent Cefdinir 1.…”