药用辅料枸橼酸三乙酯中基因毒性杂质残留量分析研究  

Genotoxic Impurity Diethyl Sulfate Residue in Pharmaceutical Excipient Triethyl Citrate

作　　者：王彩媚[1] 叶秀金[1] 陈英[1] 王淼[1] WANG Caimei;YE Xiujin;CHEN Ying;WANG Miao(NMPA Key Laboratory for Quality Control and Evaluation of Pharmaceutical Excipients,Guangdong Institute for Drug Control,Guangzhou 510663,China)

机构地区：[1]广东省药品检验所,国家药品监督管理局药用辅料质量控制与评价重点实验室,广州510663

出　　处：《中国药学杂志》2023年第19期1775-1782,共8页Chinese Pharmaceutical Journal

摘　　要：目的建立一种检测枸橼酸三乙酯中基因毒性杂质硫酸二乙酯的方法以及查看市场上枸橼酸三乙酯中硫酸二乙酯的残留情况。方法建立GC-MS测定7家生产企业共22批次枸橼酸三乙酯产品中硫酸二乙酯的残留量,并对结果进行分析。结果方法操作简单,精密度、重复性和回收率均良好;经检验,硫酸二乙酯检出率为59%,其中4批次产品硫酸二乙酯残留量超过警戒限度(0.0033%);相同生产企业不同批次产品中硫酸二乙酯残留量差异大。结论本方法可用于枸橼酸三乙酯中硫酸二乙酯的测定;22批次产品中硫酸二乙酯检出率较高,个别批次残留量超过警戒限度的7倍,提示潜在的用药安全风险较高;同一家企业生产不同批次产品其中硫酸二乙酯残留量差异大,提示生产企业应稳定生产工艺参数控制产品中的硫酸二乙酯残留量。OBJECTIVE To establish a method for detecting the genotoxic impurity diethyl sulfate in triethyl citrate and looking at the situation of diethyl sulfate residue in triethyl citrate products on the market.METHODS A GC-MS method was established for the determination of diethyl sulfate residue in a total of 22 batches of triethyl citrate products from seven manufacturing companies,and the results were analyzed.RESULTS The established method was simple to operate and showed good precision,repeatability,and recovery.Upon inspection,the detection rate of diethyl sulfate in a total of 22 batches of products from seven manufacturing firms was 59%,including four batches with diethyl sulfate residue exceeding the alert limit(0.0033%).The content of diethyl sulfate residue varied widely among different batches of products from the same manufacturing firm.CONCLUSION The method can be used for the determination of diethyl sulfate in triethyl citrate.The diethyl sulfate residue in several batches of triethyl citrate exceeded the alert limit by seven times,suggesting a potential high risk for medication safety.The manufacturing enterprises should stabilize the production process parameters to control the diethyl sulfate residue in the products.

关 键 词：硫酸二乙酯 枸橼酸三乙酯 药用辅料 气相色谱质谱联用 风险分析 

分 类 号：R917[医药卫生—药物分析学]