氨甲苯酸注射液日晒降解产物的研究  

Photodegradation products of aminomethylbenzoic acid injection

作　　者：张耀文 于明 岳青阳 刘美辰 徐万魁 ZHANG Yao-wen;YU Ming;YUE Qing-yang;LIU Mei-chen;XU Wan-kui(Liaoning Inspection,Examination&Certification Centre,Shenyang 110036;Liaoning Institute for Drug Control,Shenyang 110036)

机构地区：[1]辽宁省检验检测认证中心,沈阳110036 [2]辽宁省药品检验检测院,沈阳110036

出　　处：《中南药学》2021年第9期1915-1919,共5页Central South Pharmacy

基　　金：国家药品监督管理局2020年国家药品抽验任务(编号:73)。

摘　　要：目的对氨甲苯酸注射液的日晒降解产物进行研究。方法考察日晒对氨甲苯酸注射液有关物质和pH值的影响,建立UHPLC-Q Exactive Focus MS法对样品中产生的杂质进行结构鉴定并进行毒性预测。结果日照10 d的氨甲苯酸注射液颜色变黄,采用UHPLC-Q Exactive Focus MS推测该杂质的结构为3-羟基-4-羟甲基苯甲酸,当样品中该杂质含量超过0.1%时溶液颜色变黄,对杂质的毒性预测显示,该杂质属遗传毒性5级。结论氨甲苯酸注射液在光和热同时作用下产生杂质3-羟基-4-羟甲基苯甲酸,同时4-甲酰基苯甲酸含量和其他杂质总量明显增加,提示氨甲苯酸注射液应采用棕色安瓿包装为宜,避免阳光直射。Objective To determine the photodegradation products of aminomethylbenzoic acid injection.Methods The effect of light on the related substances and pH of aminomethylbenzoic acid injection was investigated,and the structure of impurities generated in the sample influence factor test was identified by UHPLC-Q Exactive Focus MS.Results In the influence factor test,the color of aminomethylbenzoic acid injection turned yellow after 10 days of sunshine.The structure of the impurity was inferred as 3-hydroxy-4-hydroxymethyl benzoic acid by UHPLC-Q Exactive Focus MS.When the impurity content in the sample exceeded 0.1%,the color of the solution turned yellow.Toxicity prediction showed that the genetic toxicity of 3-hydroxy-4-hydroxymethyl benzoic acid was level 5.Conclusion Under the simultaneous action of light and heat,the 3-hydroxy-4-hydroxymethyl benzoic acid was produced,the content of 4-formylbenzoic acid and other impurities may increase significantly.Therefore,aminomethylbenzoic acid injection should be protected from direct sunlight.

关 键 词：氨甲苯酸注射液 UHPLC-Q Exactive Focus MS法 3-羟基-4-羟甲基苯甲酸 毒性预测 

分 类 号：R927[医药卫生—药学]