Identification, Synthesis and Spectral Characterization of a Potential Impurity of Ceftazidime

BIN QU1,2, BEI-LI OU1,2, DE-YING CHEN1,2 AND YU-ZHU HU1,2*

1.* Department of Analytical Chemistry, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China
2. Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Tongjiaxiang 24, Nanjing 210009, China

(Received: September, 2009; Accepted: June 23, 2010)

ABSTRACT

During the process development of ceftazidime, a new impurity which exceeded the limit of 0.1% was detected by a simple HPLC method. The molecular weight of the target impurity was determined by LC/MS. This suspected impurity was synthesized and purified for characterization. When co-injected with ceftazidime in HPLC, the retention time of the impurity was the same as the ceftazidime sample containing the impurity. The structural determination of the suspected impurity was conducted by IR, MS, 1H-NMR and 13C-NMR spectroscopic techniques. This new impurity was the methyl ester of ceftazidime, and its structure was determined as (6R,7R)-7-[[(Z)-2-(2-aminothiazol-4-yl)-2-[(1-methoxycarbonyl-1-methylethoxy)imino]acetyl]amino]-8-oxo-3-[(1-pyridinio)methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate, with molecular formula of C23H24N6O7S2 and molecular weight of 560 Da.

Key words: ceftazidime, impurity, identification, synthesis, characterization