摘要
目的合成制备普鲁卡因青霉素的特定杂质2-(2-((4-((2-(二乙基氨基)乙氧基)羰基)苯基)氨基)-2-氧代-1-(2-苯基乙酰氨基)乙基)-5,5-二甲基噻唑烷-4-羧酸,该杂质为首次报道。方法以青霉素G钾盐和盐酸普鲁卡因为原料,酸性条件下合成得到含有目标杂质的粗品,之后将该粗品固体通过反相制备色谱分离、冻干12h,得到该杂质的纯化样品。结果得到纯化样品结构信息(质谱、核磁共振数据)与目标杂质相一致,总收率2.5%,LC-MS纯度89.36%,HPLC纯度80.44%。结论所得纯化样品为目标杂质2-(2-((4-((2-(二乙基氨基)乙氧基)羰基)苯基)氨基)-2-氧代-1-(2-苯基乙酰氨基)乙基)-5,5-二甲基噻唑烷-4-羧酸,可用于普鲁卡因青霉素产品的质量研究。
Objective To synthesize and prepare the specific impurity of procaine penicillin 2-(2-((4-(2-(diethylamino)ethoxy))carbonyl)phenyl)amino)-2-oxo-1-(2-phenylacetamido)ethyl)-5,5- dimethylthiazolidine-4-carboxylic acid,and the impurity was reported for the first time.Methods The crude product containing the target impurity was synthesized using the penicillin G potassium salt and the procaine hydrochloride under the acidic condition of the raw material,and then the crude solid was separated by reverse phase preparative chromatography and lyophilized for 12hours to.obtain a purified sample of the impurity.Results Structural information (MS and NMR data)of the purified sample agreed with the target impurity,which was obtained with a total yield of 2.5%,LC-MS purity of 89.36%,and HPLC purity of 80.44%.Conclusion The purified sample was the target impurity,2-(2-((4-(2-(diethylamino)ethoxy))carbonyl)phenyl)amino)-2-oxo-1-(2-phenylacetamido)ethyl)-5,5- dimethylthiazolidine-4-carboxylic acid,which could be used for the study on the quality of procaine penicillin.
作者
刘慧勤
米祥忻
吕冠芳
黄娟
王钽
严正人
王欣
Liu Hui-qin;Mi Xiang-xin;LüGuan-fang;Huang Juan;Wang Tan;Yan Zheng-ren;Wang Xin(North China Pharmaceutical Group Semisyntech Co.,Ltd,Shijiazhuang 052165)
出处
《中国抗生素杂志》
CAS
CSCD
2018年第12期1510-1513,共4页
Chinese Journal of Antibiotics
关键词
普鲁卡因青霉素
特定杂质
合成
制备分离
Procaine penicillin
Specific impurity
Synthesis
Preparation separation