LC-MS/MS测定注射用头孢噻肟钠包装所用胶塞中抗氧剂1076的迁移量

目的：建立用LC-MS/MS测定抗氧剂1076的含量测定方法。方法：采用Eclipse Plus C₈（2.1 mm×50 mm，1.8 μm）色谱柱；流动相：0.1%甲酸-甲醇（2∶98）；柱温：35℃；离子源：A-PCI源。结果：抗氧剂1076在0.269~21.52 μg·mL^-1范围内线性关系良好，相关系数为0.999 3，平均回收率为95.5%，RSD为3.5%，检出限为0.001 μg·mL^-1。结论：该方法灵敏度高，检出限低，可用于药品中抗氧剂1076的迁移量测定。

Objective: To establish a method for the determination of the content of antioxidant 1076 by the LC-MS/MS.Methods: Using ZORBAX Eclipse Plus C₈ column(2.1 mm×50 mm, 1.8 μm);Mobile phase:The 0.1% formic acid and methanol was 2:98;Column temperature was 35℃;Ion source:A-PCI source.Results: The linearity was good between 0.269 μg·mL^-1-21.52 μg·mL^-1.The correlation coefficient was 0.999 3.The average recovery rate was 95.5%, RSD was 3.5% and the detection limit was 0.001 μg·mL^-1.Conclusion: This method has high sensitivity and low detection limit, thus can be used for the determination of migration quantity of antioxidant 1076 from medicine packaging migration to drugs.

[1] 赵霞,胡昌勤,金少鸿.药用丁基胶塞中易挥发性成分的成分分析[J].药物分析杂志,2006,26(3):315 ZHAO X,HU CQ,JIN SH.The analysis of volatile substances of butyl rubber closures[J].Chin J Pharm Anal,2006,26(3):315
[2] 李兴春,路杰,李洁,等.HPLC法测定高密度聚乙烯桶包装血液透析浓缩液中抗氧剂1010、抗氧剂330、抗氧剂1076、抗氧剂168的含量[J].药学研究,2016,35(2):86 LI XC,LU J,LI J,et al.Determination of antioxidant 1010,antioxidant 330,antioxidant 1076 and antioxidant 168 in high density polyethylene barrels for blood dialysis concentrate packing by HPLC[J].J Pharm Res,2016,35(2):86
[3] 黄萍,刘兴兰.SPE-HPLC法测定三层共挤输液袋中抗氧剂在氧氟沙星氯化钠注射液中的迁移量[J].中国药师,2016,19(12):2267 HUANG P,LIU XL.Determination of antioxygen migration amount in ofloxacin and sodium chloride injection from three-layer coextrusion infusion bags by SPE-HPLC[J].China Pharm,2016,19(12):2267
[4] 张芦燕,王曼泽,王翔宇.聚丙烯瓶装氯化钠注射液中抗氧剂迁移量的测定[J].西北药学杂志,2013,28(6):583 ZHANG LY,WANG MZ,WANG XY,et al.Determination of the migration of antioxidant in sodium chloride injections packed by polypropylene infusion bottles[J].Northwest Pharm J,2013,28(6):583
[5] 陈晓雨,李银峰,林秀云等.LC-MS技术在化学药杂质分析中的研究进展[J].现代药物与临床,2014,29(6):696 CHEN XY,LI YF,LIN XY,et al.Research progress on analysis on impurity in chemical drug by LC-MS technology[J].Drugs Clin,2014,29(6):696
[6] 冼燕萍,郭新东,穆同娜,等.食品接触塑料容器中限用荧光增白剂184和393的迁移行为研究[J].质谱学报,2014,35(6):530 XIAN YP,GUO XD,MU TN,et al.Study on migration of the restricted fluorescent whitening agent 184 and 393 in food contact plastic container[J].J Chin Mass Spectrom Soc,2014,35(6):530
[7] 王文刚,吴艳,暴铱,等.新型载药容器中添加剂的提取试验研究[J].解放军药学学报,2016,32(3):215 WANG WG,WU Y,BAO Y,et al.Extraction of additives in drug loading container of a novel syringe[J].Pharm J Chin PLA,2016,32(3):215
[8] 朱碧君,胡红刚,李婷婷,等.HPLC法测定聚丙烯输液瓶中抗氧剂1010、抗氧剂1076、抗氧剂168、抗氧剂330的含量[J].药物分析杂志,2012,32(3):416 ZHUI BJ,HU HG,LI TT,et al.HPLC determination of antioxidant 1010、antioxidant 1076、antioxidant 168 and antioxidant 330 in polypropylene infusion bottles[J].Chin J Pharm Anal,2012,32(3):416
[9] 王悦雯,陈蕾,冯靖,等.三层共挤输液用袋的添加剂测定和迁移量测定[J].药物分析杂志,2016,36(1):138 WANG YW,CHEN L,FENG J,et al.Determination of additives of three-layer co-extrusion bags used for infusion and the migration of additives[J].Chin J Pharm Anal 2016,36(1):138
[10] EP 5.0[S].2010:282
[11] 林晨煦,高丹玲.注射用头孢唑林钠与卤化丁基胶塞相容性的加速试验[J].海峡药学,2011,23(1):54 LIN CX,GAO DL.Acceleration test of compatible of cefazolin sodium for injection and halogenated butyl rubber stopper[J].Strait Pharm J,2011,23(1):54
[12] 刘成红,魏立平,罗小茹,等.注射用盐酸头孢替安与胶塞相容性研究[J].药物评价研究,2014,37(5):420 LIU CH,WEI LP,LUO XR,et al.Compatibility between rubber closures and cefotiam hydrochloride for injection[J].Drug Eval Res,2014,37(5):420
[13] 胡长鹰,黄有红.HDPE膜中抗氧剂1076向替代脂肪类食品模拟物迁移的研究[J].食品工业科技,2009,30(02):244 HU CY,HUANG XH.Study on migration of antioxidant 1076 from HDPE film to fatty food simulacrum[J].Sci Technol Food Ind,2009,30(02):244
[14] 赵霞,胡昌勤,金少鸿.对考察药用丁基胶塞与药物相容性的思考与建议[J].中国药事,2007,21(10):810 ZHAO X,HU CQ,JIN SH.Consideration and suggestion to estimate the compatibility between rubber closures and drugs[J].Chin Pharm Aff,2007,21(10):810
[15] 李立根,张毅兰.药用胶塞及其与药品的相容性简述[J].中国医药工业杂志,2015,46(12):1366 LI LG,ZHANG YL.Review of rubber stoppers for pharmaceutical use and its compatibility with pharmaceutical products[J].Chin J Pharm,2015,46(12):1366