Analytical Sciences

Identification and Characterization of New Degradation Products of Cefepime Dihydrochloride Monohydrate Drug Substance during Stress Stability Studies

Vundavilli JAGADEESH KUMAR,* P. BADARINADH GUPTA,* Kothapalli S. R. PAVAN KUMAR,* Korrapati V. V. PRASADA RAO,* K. Ranga RAO,* S. John PRASANNA,* Hemant KUMAR SHARMA,* and K. MUKKANTI**

*Aurobindo Pharma Ltd., Research Centre, 313, Bachupally, Qutubullapur Mandal, Hyderabad 500090, Andhra Pradesh, India
**J. N. T. University, Kukatpally, Hyderabad 500085, Andhra Pradesh, India

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 (¹H NMR, ¹³C 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.

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