Structural identification and characterization of impurities in ceftizoxime sodium.
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.
Bharathi
Ch
Ch
A.P.L. Research Centre, 313, Bachupally, Hyderabad 500072, India.
Prasad
Ch S
ChS
Bharathi
D Vijaya
DV
Shankar
Rama
R
Rao
V Janardhana
VJ
Dandala
Ramesh
R
Naidu
A
A
D000900:Anti-Bacterial Agents / Q000032:analysis*; D015296:Ceftizoxime / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004340:Drug Contamination; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000592:standards; D011786:Quality Control; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods; D013678:Technology, Pharmaceutical
D000900:Anti-Bacterial Agents; D004364:Pharmaceutical Preparations; D015296:Ceftizoxime