罗米地辛潜在杂质的分离与鉴定（英文）  

Isolation and Identification of Potential Impurities of Romidepsin

作　　者：熊磊[1] 闵涛玲[1] 陈昌发[1] 胡海峰[1] XIONG Lei;MIN Taoling;CHEN Changfa;HU Haifeng(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]中国医药工业研究总院上海医药工业研究院创新药物与制药工艺国家重点实验室

出　　处：《中国医药工业杂志》2019年第12期1413-1422,共10页Chinese Journal of Pharmaceuticals

基　　金：supported by industries, universities and research cooperation project of Shanghai(No.cxy-2013-53)

摘　　要：罗米地辛是1种抗肿瘤抗生素,最初是从紫色色杆菌(Chromobacterium violaceum)NO.968中分离得到的。首先,使用HPLC法对罗米地辛原料药进行分析,检测到7个杂质,含量0.06%~0.23%。然后,通过反相制备液相获得以上杂质,分别命名为杂质-1、杂质-2、杂质-3、杂质-4、杂质-5、杂质-6和杂质-7。最后,通过1D(1H、13C、DEPT-135)、2D(HSQC、HMBC、1H-1H COSY)核磁数据以及质谱数据确定上述杂质的化学结构。结果表明,杂质-1和杂质-2分别在C-22位和C-17位上比罗米地辛相应位置少2个甲基。杂质-3、杂质-4和杂质-5分别在C-22、C-17和C-20位较罗米地辛相应位置少1个甲基。杂质-6含有1个三硫键,而杂质-7在C-22位上比罗米地辛相应位置多1个亚甲基。这些杂质可能是罗米地辛生物合成过程中的副产物,同时本研究对发酵过程中产生杂质的关键因素进行了考察。Romidepsin is an antitumor drug isolated from the fermentation broth of Chromobacterium violaceum NO.968. Seven impurities with the concentration range from 0.06% to 0.23% in romidepsin bulk drug were detected by HPLC. These impurities, named as Impurity-1, Impurity-2, Impurity-3, Impurity-4, Impurity-5, Impurity-6 and Impurity-7, were isolated from romidepsin bulk drug by reverse phase preparative HPLC. Their molecular structures were confirmed by 1 D(1 H, 13 C, DEPT-135), 2 D(HSQC, HMBC and 1H-1H COSY) NMR spectra and MS data. Compared with the chemical structure of romidepsin, Impurity-1 and Impurity-2 lacked two methyl groups at C-22 and C-17, respectively;Impurity-3, Impurity-4 and Impurity-5 lost one methyl group at C-22, C-17 and C-20, respectively;Impurity-6 contained a trisulfide bond and Impurity-7 possessed an additional methylene group at C-22. All these impurities might be the byproducts of the biosynthesis pathway of romidepsin and some key factors in the fermentation process that related to the formation of impurities were studied herein.

关 键 词：罗米地辛 杂质 分离 结构解析 

分 类 号：R979.1^+4[医药卫生—药品]