Analysis And Control Of Impurity Profile Of Cefotaxime Sodium

Cefotaxime sodium,was clinically used in a variety of sensitive bacteria infections.In this paper,the impurity profile and color stability of Cefotaxime sodium are systematically studied,in view of the unknown Impurity X whose content is more than 0.10% in product of North China Pharmaceutical Co.,Ltd.The analysis results can help to improve perfect the manufacturing process,making the product quality conform to the demands of the FDA and ICH.And it also can be used as a basic support of DMF files,providing theoretical and data foundations for international registration and the entry of international standard market.Current Chinese pharmacopoeia and European pharmacopoeia chromatographic conditions were adopted to carry on the separation and analysis of cefotaxime sodium sample based on HPLC method.The two methods were compared by verifying specificity,system suitability.The results show that the European pharmacopoeia check method for relevant materials of cefotaxime sodium(Method Two)possesses high sensitivity,good reproducibility and accuracy.At the same time,impurities profile of cefotaxime sodium was obtained,and among them,five kinds of impurities are of more than 0.10%,including unknown impurity X.Combined with the actual production process,potential impurities in cefotaxime sodium product were speculated.According to chromatographic retain information,existing standard of raw materials or intermediates sample were analysed alone by Method Two.With LC-MS,IR,NMR and other information to confirm the structure of the five kinds of target impurities,the structure information of unknown impurity X was obtained.At the same time the Method Two was confirmed to be more applicable for the determination of cefotaxime dimer.On the basis of molecular exclusion mechanism,gel chromatography in current Chinese pharmacopoeia was used by the transformation of the two kinds of mobile phase,in order to quantitatively assay the content of cefotaxime dimer with external standard method,using cefotaxime sodium standard material as the reference substance.The determination results show low measurement value,large deviation and poor reproducibility.The Method Two shows high sensitivity,good reproducibility,high accuracy,short time-consuming,less sample weight,simultaneous separation analysis and determination of dimer,and the effective control of the content of dimer.Different accelerated experiments were designed.With regard to cefotaxime sodium solution for test under different damage degrees,the grade of color stability was investigated according to the solution color comparison method and ultraviolet spectrophotometric method.The rate and pathways of degradation in different environments were determined according to the Method Mwo by investigating content variation of impurities.It is found that the color level stability of cefotaxime sodium has some relationship with its impurity profile to some degree.The drug should be insulated from water,high temperature,light,acid,alkali,oxidant condtions in the process of production or storage,so as to guarantee the quality of medicines.The Method Two can be used for the entire analysis of the impurity profile of cefotaxime sodium,which can be used to investigate impurities,dimer,color stability of cefotaxime sodium at the same time.