药用辅料三氯叔丁醇有关物质检查方法研究及标准制定  

Investigation on determination of related substances of pharmaceutical excipient chlorobutanol andquality standard established

作　　者：张志军 张喆 王铁松 吴科春 胡琴 戴红 ZHANG Zhijun;ZHANG Zhe;WANG Tiesong;WU Kechun;HU Qin;DAI Hong(Beijing Institute For Drug Control,NMPA Key Laboratory for Research and Evaluation of Genetic Drugs,Beijing Key Laboratory of Analysis and Evaluation on Chinese Medicine,Beijing 102206,China)

机构地区：[1]北京市药品检验研究院国家药品监督管理局仿制药研究与评价重点实验室,北京102206

出　　处：《中国药品标准》2022年第5期498-504,共7页Drug Standards of China

摘　　要：目的:建立三氯叔丁醇有关物质测定的气相色谱分析法,对该辅料质量标准进行修订。方法:以聚乙二醇(PEG-20M)为固定液的毛细管柱。起始温度为35℃,保持5 min,以20℃·min^(-1)的速率升温至135℃并保持10 min;检测器温度为280℃;进样口温度为260℃。检测器分别为FID(丙酮)和ECD(三氯甲烷);进样分别采用顶空进样(丙酮)和直接进样1μL(三氯甲烷);顶空平衡温度90℃,平衡时间为20 min。结果:丙酮和三氯甲烷分别在0.5~40μg·mL^(-1)和5~500 ng·mL^(-1)范围内峰面积与浓度呈良好的线性关系(r值分别为0.9997和0.9995);丙酮和三氯甲烷平均回收率分别为93.9%.和106.9%,均符合方法学研究要求;按该方法对2批样品进行有关物质检查,丙酮含量分别为0.008%和0.004%,三氯甲烷含量分别为0.0008%和0.0003%。结论:建立方法可增订入中国药典质量标准,用于三氯叔丁醇质量控制。Objective:To establish a gas chromatography method for the determination of related substances of trichlorotert butyl alcohol,and revise the quality standard of the excipient.Methods:A capillary column with polyethylene glycol(PEG-20M)as the fixing solution.The initial temperature was 35℃and kept for 5 min.The temperature was raised to 135℃at a rate of 20℃·min^(-1) and kept for 10 min.The temperature of the detector was 280℃.The inlet temperature was 260℃.The detectors were FID(acetone)and ECD(trichloromethane).Headspace injection(acetone)and direct injection of 1μL(trichloromethane)were used for injection.The headspace equilibration temperature was 90℃and the equilibration time was 20 min.Results:There were a good linear relationship between peak area and concentration in the concentration range of 0.5-40μg·mL^(-1)(acetone)and 5-500 ng·mL^(-1)(chloroform)(r values were 0.9997 and 0.9995 respectively);the average recoveries of acetone and chloroform were 93.9%and 106.9%respectively.All meet the requirements of methodological research.Determine two samplesunder this method,the content ofacetone were 0.008%and 0.004%,and the content of chloroform were 0.0008%and 0.0003%respectively.Conclusion:The method can be added into the quality standard of the Chinese pharmacopoeia for the quality control of chlorobutanol.

关 键 词：三氯叔丁醇 有关物质 中国药典 质量标准修订 气相色谱 

分 类 号：R921.2[医药卫生—药学]