Process Synthesis And Impurity Research Of Carbenicillin Disodium

Carbenicillin disodium is a semi-synthetic anti-Pseudomonas penicillin with broad-spectrum. This thesis mainly engages in improving synthetic reaction of carbenicillin disodium, including benzene malonic acid compound synthesis process research, and6-APA and benzyl malonic acid compound condensation technology research, in order to have a new process suitable for the industrialization.The synthesis process technology was optimized on the basis of orthogonal design and analysis of variance. The yield was chosen as index,reaction time,reaction temperature and BF3/Et2O were factors. On the basis of this, combining the actual production situation to optimization process. At last, the best synthesis process was that BF3/Et2O10%,reaction time15-18h,reaction temperature5～℃,and made a result that the yield was94.97%. Long-term and accelerated stability test showed that, in the specified storage conditions, benzyl malonic acid compound was stable, the quality indicators were no significant change.Benzyl malonic acid compounds as the side chain, and condensation with6APA. The condensation heat preservation time, dehydration process, temperature of the NaHCO3adjust pH and rejection filter technology were studied. The optimal process shorten the production time greatly, and improve the production quality. Both of the pilot production and the large scale production quality were compliance with the requirements. Long-term and accelerated stability test of carbenicillin disodium showed that, its quality was stable, the new condensation process of carbenicillin disodium was suitable for industrialized production. And long-term and accelerated stability test of sterile carbenicillin disodium also proved it.Impurity research contains:Look for appropriate conditions of liquid ChromatograpHy by HPLC; Determine preliminary its chemical structure by HPLC-MS; Separate an purify the impurity by preparation HPLC.