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xizj(金币+1): 谢谢参与
西湖醉鱼: 金币+10, ACI+1 2019-08-07 17:48:48
1、欧洲有指导原则规定了工艺中副产物产生苯或者使用了其他可能引入苯的溶剂，需要对苯进行控制，“Benzene in an active substance can be a by-product from a chemical reaction (for example, grignard reaction, when phenylmagnesium halide used in excess is hydrolysed to yield benzene), or may arise from another solvent, for example, toluene or acetone where benzene is a known process impurity.”具体如何控制，苯是否必须订入终产品质量标准，该指导原则有详细规定--Annexes to:CPMP/ICH/283/95 Impurities: Guideline for residual solvents &CVMP/VICH/502/99 Guideline on impurities: residual solvents
2、可能引入苯的溶剂除了甲苯、丙酮，乙醇也有可能带入，详见“2011年度CEP申请审评十大缺陷”Top 6:“Some solvents (e.g. acetone, toluene, ethanol, methanol, isopropanol, xylene, hexane and petroleum ether) may be contaminated with Class 1 solvents (e.g. benzene). Therefore, when these solvents are used in the manufacturing process of the final substance and in particular in the purification steps, potential residues of their contaminant in an intermediate or in the final substance should be addressed.”
PS: 如果贵公司的乙醇制备工艺非化学合成，不会带入苯，比如糖发酵，可不用考虑乙醇带入苯的风险
3、ChP、EP、USP中乙醇各论均有对苯进行控制 |
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