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

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 (1H NMR, 13C 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]]-4-oxoazetidin-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.

Identification and characterization of degradation products of dicloxacillin in bulk drug and pharmaceutical dosage forms.

Impurity profiling of dicloxacillin sodium bulk drug and pharmaceutical dosage forms subjected to stability studies is evaluated. Of many impurities detected in HPLC analysis, three were not reported in the literature. The impurities have been identified by LC-MS; isolated by preparative HPLC; and characterised by NMR, Mass spectroscopy and IR. Pure impurities obtained by isolation were co-injected with dicloxacillin sodium sample to confirm the retention times in HPLC. Structure elucidation of these degradation products by spectral data has been discussed in detail.