Identification and characterization of new degradation products of cefepime dihydrochloride monohydrate drug substance during stress stability studies

Anal Sci. 2010;26(10):1081-6. doi: 10.2116/analsci.26.1081.

Abstract

The degradation products of Cefepime dihydrochloride that emerged throughout stress stability studies have been determined, identified and characterized. The two new impurities were detected by gradient reverse-phase high performance liquid chromatography (HPLC), and Impurity-I was formed in the range from 0.2 to 11.0% and Impurity-II range from 0.2 to 3.5%. These impurities have been identified by LC/MS, and were not reported in the literature. These impurities were synthesized, isolated and characterized. Based on the spectral data, the impurities were named (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3-[(1-methyl-1-pyrrolidinium)methyl]-3-cephem-4-carboxylate-1-oxide (Impurity-I); (2RS)-2[[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]-methyl]-1,2,5,7-tetrahydro-7-oxo-4H-furo[3,4-d][1,3]thiazine (Impurity-II). The structures were established unambiguously by independent synthesis and co-injection in HPLC to confirm the retention times and relative retention times. The structural elucidation of these impurities by spectral data ((1)H NMR, (13)C NMR, 2D-NMR (COSY, HSQC and HMBC), LC/MS, TOF-MS, elemental analysis and IR), synthesis, isolation and the formation of these impurities are discussed in detail.

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Cefepime
  • Cephalosporins / analysis*
  • Cephalosporins / chemistry
  • Drug Contamination
  • Drug Stability
  • Furans / analysis*
  • Furans / chemistry
  • Hot Temperature
  • Molecular Structure
  • Oxidation-Reduction
  • Photolysis
  • Thiazines / analysis*
  • Thiazines / chemistry

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • Furans
  • Thiazines
  • Cefepime