Study on preparation process of high purity gentamicin C1a free base
Yang Tao;Chen Zhou-zhou;Wang Hai-dong;Li Ya-jun;Li Ji-an;Lei Xiang-xiao;Chen Dai-jie;Chu Xiao-he;School of Pharmacy, Shanghai Jiao Tong University;Yangtze River Delta green Collaborative Innovation Center,Zhejiang University of technology;Changzhou Fangyuan Pharmaceutical Co., Ltd.;State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry;
Objective To purify the starting material of etimicin sulfate, gentamicin C1 a(HPLC purity 91%～93%) by macroporous adsorption resin chromatography and the salting out crystallization method, thereby reducing the impurity level of etimicin from gentamicin C1 a. Methods The adsorption capacity and elution parameters of gentamicin C1 a purified by the macroporous adsorption resin were investigated by the adsorption amount of gentamicin C1 a and the purity of gentamicin C1 a. Based on the purity and the salting out yield of gentamicin C1 a sample after salting out, the optimum temperature, solvent, acid addition amount and acid type of salting-out process were investigated. Results The superior resin NM200 was obtained, and the preferred analytical solution had a pH of 2.0 and a flow rate of 0.5 BV/h. After optimization, the purification yield increased from 65% to 74%. Through salting-out crystallization conditions screening and optimization, it was determined that the conditions of adding sulfuric acid(pH6.5) and methanol and ethanol 1:2 were better after adding solvent at room temperature. The purity of gentamicin C1 a obtained after optimization was 98.2%, and the yield was more than 93%. A variety of inorganic acid precipitation crystals were studied, and it was found that white solids were precipitated under the conditions of phosphoric acid, sulfuric acid and carbonic acid. Conclusion By comparing the purification connection of the macroporous adsorption resin and the salting out crystallization, the purity of gentamicin C1 a free base obtained after combination and purification is greater than 99.0%, which is more than 6% higher than the sample before purification, and the yield is more than 70%.
【CateGory Index】： TQ460.6