Identification, isolation and characterization of a new impurity in cefoxitindrug substance resulting from stress stability studies

Abstract

A new unknown impurity of cefoxitin formed during a gradient reverse phase high performance liquid chromatography (HPLC) analysis of stress stability samples of the drug substance cefoxitin, and the level of this impurity was found at up to 0.9%. This impurity was identified by LC-MS and characterized by ( 1 H NMR, 13 C NMR, LC/MS/MS, elemental analysis and FT-IR). Based on the spectral data, the impurity was named as, 3-[[(2R,3S)-[3-methoxy-3-N-[2-(thiophen-2-yl)acetamido]]-4oxoazetidin-2-ylthio]-2-[(carbamoyloxy)methyl]]-acrylic acid. The structure of this impurity was also established unambiguously, prepared by isolation and co-injected into HPLC to confirm the retention time. To the best of our knowledge, this impurity has not been reported elsewhere. Structural elucidation of the impurity by spectral data is discussed in detail.

Preparation of Three Impurities in Cefoxitin

“…5 Vundavilli and co-workers also reported an impurity in cefoxitin resulting from stress stability studies. 6 Owing to the poor stability of cephalosporins, the synthesis of impurities can be difficult. The structures and simplified names of three of the impurities, 2, 3 and 4, are shown in Fig 1, none of which are available commercially and no preparation method has been reported.…”