| Nowadays,cephalosporin antibiotics have been widely used in clinical treatment of disease which were caused by pathogenic bacteria,and they have been developed into the fourth-generation.Cefaclor belongs to the second-generation cephalosporins,and it is also in great demand for its potent biological activity.This paper briefly introduces the synthesis methods of cefaclor and its clinical applications,summarizing the synthesis process and current detection methods of 7-amino-3-chloro-3-cephem-4-carboxylic acid(7-ACCA)at home and abroad,which is the key intermediate of cefaclor.This project is entrusted to solve problems of 7-ACCA,the intermediate of cefaclor,in the production of quality control and product control.7-ACCA,is synthesized from penicillin potassium by separate six-step reaction.In the paper,based on characteristics of chemical reaction of each step,the effect of mobile phase,flow rate,column temperature and the detection wavelength are investigated in detail,and HPLC methods for the mother liquor and the product are established successfully.Linear range,precision,detection limit and accuracy are researched one by one,at the same time,the feasibilities of the methods are examined in the actual production,which are described below.In the first step of the synthesis of 7-ACCA,based on the structure of the reactant otassium penicillin and product GESO,the HPLC methods were successfully established for the determination of GEO residual in the mother liqour and this step product,and that the methods have been used to the real production process.In the second step of the synthesis of 7-ACCA,based on the structure of the reactant GESO and product AEX,the HPLC methods were successfully established for the determination of residual GESO in this step mother liqour and product,also the methods have been used to the real production process.In the third step of the synthesis of 7-ACCA,based on the structure of the reactant AEX and product AEN,the HPLC methods were also successfully established for the determination of residual of AEX in this step mother liqour and product,and the methods have been used to the real production.In the fourth step of the synthesis of 7-ACCA,the HPLC methods were also successfully established for the determination of residual of reactant AEN in the mother and the product CHS,similarly,the methods have been used to the real production.In the fifth step of the synthesis of 7-ACCA,the HPLC methods were also successfully established for the determination of residual of reactant CHS in the mother and the product RS,similarly,the methods have been used to the real production.In the sixth step of the synthesis of 7-ACCA,the HPLC methods were also successfully established for the determination of residual of reactant RS in the mother and the product 7-ACCA,similarly,the methods have been used to the real production.In a word,all of the methos have been used for the determination of six steps reactant mother liqours and products at least more than half a year,compared to the traditional method of thin layer chromatography(TLC),the presents methods were proved to be sensitive,acurate and feasible in the actual productin,and it made the production with more yield,less cost,and promote the competitiveness of the enterprise In the domestic and foreign markets,and also ascertain the production continuity and all of products quality of 7-ACCA. |