Ceftizoxime sodium is a parenteral beta-lactamic antibacterial drug. In the synthesis of ceftizoxime sodium, eight process related impurities were detected in HPLC analysis. Pure impurities obtained by both synthesis and preparative HPLC were co-injected with ceftizoxime sample to confirm the retention times in HPLC. The impurities were characterized as, (6R,7R)-7-amino-3-cephem-4-carboxylic acid (impurity I); (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3-cephem-1-oxo-4-carboxylic acid (impurity II); (4RS,6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino) acetamido]-3,4-dihydro-3-cephem-4-carboxylic acid (impurity III); (6R,7R)-7-[(E)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylic acid (impurity IV); (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3-cephem-N-(3-cephem-4-carboxy-7-yl)-4-carboxamide (impurity V); (6R,7R)-7-[(Z)-2-[[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetylamino]thiazol-4-yl]-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid (impurity VI); 2-mercaptobenzothiazole (impurity VII) and 2-mercapto benzothiazolyl [(Z)-2-(2-amino-4-thiazolyl)-2-methoxyimino] acetate (impurity VIII). Structural elucidation of all impurities by spectral data ((1)H NMR, (13)C NMR, MS and IR) has been discussed.