Cefepime hydrochloride hydrate

The pseudo first-order rate constants and thermodynamic parameters for the decomposition of cefepime in solid state in absence of humidity and at a relative humidity of 76.4% were calculated. The effect of humidity on the stability of cefepime dihydrochloride monohydrate in the humidity range 25.0%-76.4% at 358 K is described by the equation ln ki = (0.031 +/- 0.0043) x RH% - 10.08 +/- 0.22.

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.