药用丁基胶塞中抗氧剂264、1010、5057迁移研究  

Migration studies on the common antioxidants in rubber plug

作　　者：浦雨伟 崔萍[1,2] 吴娟[1] 丁逸梅[1,2] PU Yu-wei CUI Ping WU Juan DING Yi-mei(School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, China Jiangsu Provincial Institute of Material Medica, Nanjing Tech University, Nanjing 210009, China)

机构地区：[1]南京工业大学药学院,南京210009 [2]南京工业大学江苏省药物研究所有限公司,南京210009

出　　处：《药物分析杂志》2016年第12期2231-2240,共10页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立高效液相色谱法同时测定药用丁基胶塞中的抗氧剂264、抗氧剂1010和抗氧剂5057。方法:采用HPLC法对抗氧剂264(2,6-二叔丁基-4-甲基苯酚)、抗氧剂1010{四[β-(3,5-二叔丁基-4-羟基苯基)丙酸]季戊四醇酯}和抗氧剂5057(丁基或辛基取代的二苯胺)的迁移量进行研究;使用Inertsil ODS C_(18)色谱柱(4.6 mm×150 mm,5μm),以甲醇为流动相A,10 mmol·L^(-1)乙酸铵溶液为流动相B,梯度洗脱,流速1.0 m L·min^(-1),检测波长220 nm(检测抗氧剂264和抗氧剂1010)、280 nm(检测抗氧剂5057);利用LC-MS/MS方法进行鉴别,采用三重四极杆质谱检测器、电喷雾离子源ESI,以正负离子模式扫描,质量数扫描范围m/z 50~1 500。结果:浸提试验确证了胶塞中含有的抗氧剂。几种抗氧剂的分离度良好,抗氧剂5057无明显降解产物,抗氧剂264与抗氧剂1010的降解产物均能与各自主峰分开,抗氧剂264、1010、5057的检出限分别为0.081、0.061、0.062μg·m L^(-1),且在各自的线性范围内线性关系良好(r=0.999 6~0.999 9,n=5),平均回收率均在98%~102%。5个企业的20批样品中均未检出抗氧剂。结论:建立的方法可用于对胶塞中抗氧剂264、1010、5057进行迁移研究。Objective： To establish an HPLC method for determination of the antioxidant 264 （2, 6-di-tert-butyl-4-methylphenol）, antioxidant 1010 （pentaerythritol tetrakys 3-3, 5-ditert-butyl-4-hydroxyphenyl）propionate） and antioxidant 5057 （butyl-substituted or octyl-substituted diphenylamine）.Methods： The content of the antioxidant 264, antioxidant 1010 and antioxidant 5057, which were transfered to the sample from the contact materials was determined by Helution.The detection wavelength was 220 nm （detection for antioxidant 264 and antioxidant 1010） and 280 nm （detection for antioxidant 5057）, the flow rate was 1.0 mL·min-1, and the column temperature was 35℃.The main degradation products of antioxidants were identified by LC-MS/MS with a triple-quadrupole mass spectrometer.The compounds were ionized in the electrospray ionization （ESI） and operated in both positive and negative modes;the mass scanning range was m/z 50-1 500.Results： The antioxidants in rubber stopper could be confirmed by leaching tests.The antioxidants could be separated effectively from each other.There was no obvious ingredients of antioxidant 5057 and the degradation products of antioxidant 264 and antioxidant 1010 also could be separated with its main peak.The detection limit of antioxidant 264, 1010 and 5057 were 0.081, 0.061, 0.062 μg·mL-1, respectively.The calibration curves of the antioxidants were linear in the self-concentration range （r=0.999 6-0.999 9;n=5）, and the recoveries of antioxidant 264, antioxidant 1010 and antioxidant 5057 were in the range of 98% to 102%.After testing 20 batches of samples from 5 manufacturers, no migratory antioxidant was detected.Conclusion： The established method can be used for quality control of antioxidants 264, 1010, 5057 in rubber stopper.

关 键 词：丁基胶塞 药瓶密封材料 药品包装材料 2  6-二叔丁基-4-甲基苯酚 四[β-(3  5-二叔丁基-4-羟基苯基)丙酸]季戊四醇酯 丁基或辛基取代的二苯胺 抗氧剂 聚合物稳定剂 抗氧剂降解产物 抗氧剂迁移 药物相容性 质量控制 高效液相色谱 液相色谱-串联质谱 

分 类 号：R917[医药卫生—药物分析学]