多拉菌素有机杂质的纯化与结构鉴定  

Isolation and identification of impurities in doramectin

作　　者：金鑫 秦娜 范思洋[2] 杨玉雷[2] 郭雅俊 Jin Xin;Qin Na;Fan Siyang;Yang Yulei;Guo Yajun(Zhejiang Jinhua Conba Bio-pharm Co.,Ltd.,Jinhua 321016;State Key Lab of New Drug&Pharmaceutical Process,Shanghai Institute of Pharmaceutical Industry,China State Institute of Pharmaceutical Industry,Shanghai 201203)

机构地区：[1]浙江金华康恩贝生物制药有限公司,金华321016 [2]上海医药工业研究院有限公司,中国医药工业研究总院有限公司,创新药物与制药工艺国家重点实验室,上海201203

出　　处：《中国抗生素杂志》2023年第8期900-911,共12页Chinese Journal of Antibiotics

摘　　要：目的分离与鉴定多拉菌素中有机杂质,对改进生产工艺,提高产品质量具有重要意义。方法采用制备液相色谱技术,对多拉菌素中有机杂质进行分离制备,并通过质谱和核磁共振技术鉴定杂质结构。结果经制备液相分离得到5个主要杂质,经核磁共振光谱和质谱分析鉴别为12-乙基多拉菌素,14-去甲基多拉菌素,5-甲氧基多拉菌素,5-酮多拉菌素和25-环己基-阿维菌素B2。其中12-乙基多拉菌素未见文献报道。结论建立了多拉菌素有机杂质的制备方法,并进行了结构鉴定,为多拉菌素的质量控制提供了参考。Objective To separate and identify main organic impurities in doramectin and improve the production process and product quality.Methods The organic impurities of doramectin were enriched by the semi-preparative liquid chromatography.The nuclear magnetic resonance spectrum and mass spectrum analysis were used to identify the structures of the impurities.Results Five impurities were obtained by the preparative liquid chromatography.By MS and NMR analysis,the impurities were identified as 12-ethyldoramectin,14-demethyldoramectin,5-methoxydoramectin,5-ketodoramectin,and 25-cyclohexy-avermectin B2.12-ethyldoramectin was newly identified.Conclusion The method of preparing organic impurities was developed,and the structures were identified.This research provides a reference for the quality control of doramectin.

关 键 词：多拉菌素 分离制备 杂质 结构鉴定 高效液相色谱 质谱 核磁共振 

分 类 号：R978.1[医药卫生—药品]