Identification, Structural Elucidation and Validation of HPLC Method for the Determination of New Impurities in Ceftazidime Drug Substance

Author(s): N. Rashmitha, P. Badarinadh Gupta, T. Joseph Sunder Raj, Rama Shankar, Hemant Kumar Sharma and K. Mukanti

Ceftazidime is a third generation semi-synthetic cephalosporin antibiotic drug. During the analysis of ceftazidime commercial batches, three unknown impurities other than those specified in European Pharmacopeia were detected in HPLC analysis at levels ranging from 0.05 to 0.2%. These unknown impurities were isolated by preparative HPLC and co-injected with ceftazidime sample to confirm the retention times in HPLC. Structural elucidation of these impurities [Impurity-I ((6R,7R)-7-[(Z) -2-(2-Aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-(1-pyridiniummethyl)-3-cephem-4- carboxylate sulfoxide), Impurity-II ((6R,7R)-7-[(Z)-2-(2-N-Formylaminothiazol-4-yl)-2-(2-carboxy-prop- 2-oxyimino)-acetamido]-3-(1-pyridiniummethyl)-3-cephem-4-carboxylate), and Impurity-III ((6R, 7R)-7- [(Z)-2-(2-Amino-thiazol-4-yl)-2-(2-carboxyprop-2-oximino)acetamido]-3-hydroxymethyl-3-cephem-4- car boxylic acid lactone)] by spectral data (1H NMR, 13C NMR, IR and MS) has been discussed. The developed RP-LC method was validated with respect to linearity, accuracy, precision and high sensitivity with detection limits and quantification limits ranging from 0.13 μg/mL to 0.142 μg/mL and 0.260 μg/mL to 0.284 μg/mL, respectively.

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