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

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 ran...

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Bibliographic Details
Published in:Analytical Sciences 2010/10/10, Vol.26(10), pp.1081-1086
Main Authors: KUMAR, Vundavilli JAGADEESH, GUPTA, P. BADARINADH, Kothapalli S. R. PAVAN KUMAR, Korrapati V. V. PRASADA RAO, RAO, K. Ranga, PRASANNA, S. John, SHARMA, Hemant KUMAR, MUKKANTI, K.
Format: Article
Language:English
Subjects:
Analytical Chemistry
Anti-Bacterial Agents - chemistry
Cefepime
Cephalosporins - analysis
Cephalosporins - chemistry
Chemistry
Drug Contamination
Drug Stability
Furans - analysis
Furans - chemistry
Hot Temperature
Molecular Structure
Oxidation-Reduction
Photolysis
Thiazines - analysis
Thiazines - chemistry
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Summary: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.
ISSN:0910-6340
1348-2246
1348-2246
DOI:10.2116/analsci.26.1081