药品包装材料用塑料粒料中8个常用抗氧剂的含量测定

目的：建立可同时测定药品包装材料用塑料粒料中8个常用抗氧剂（抗氧剂245、抗氧剂1178、抗氧剂264、抗氧剂3114、抗氧剂1010、抗氧剂330、抗氧剂1076、抗氧剂168）的含量测定方法，并对市售的多家药包材生产企业所使用的塑料粒料中的抗氧剂含量进行考察。方法：以乙腈为提取溶剂，利用高效液相色谱法对塑料粒料中的抗氧剂含量进行测定，色谱柱为Diamonsil C₁₈（150 mm×4.6 mm，5 μm），流动相为乙腈-水，梯度洗脱，流速1.5、1.8 mL·min^-1，检测波长224 nm。结果：本方法可快速有效地分离测定8个常用抗氧剂。各抗氧剂在相应的浓度范围内线性关系良好，回收率符合要求。通过收集25种不同来源塑料粒料，并测定其中的抗氧剂含量，汇总后便于日后进行药包材原料的选择。结果检测出抗氧剂1178、抗氧剂264、抗氧剂1010、抗氧剂330、抗氧剂1076、抗氧剂168含量范围分别为0.012%~0.046%、0%~0.016%、0.002%~0.012%、0.003%~0.086%、0.007%~0.081%、0.006%~0.057%。结论：本文建立的塑料粒料中抗氧剂的检测方法简便，准确，可用于考察塑料粒料中8个常用抗氧剂的含量及质量控制。

Objective: To establish a method for simultaneous determination of 8 kinds of commonly used antioxidants(antioxidant 245,antioxidant 1178,antioxidant 264,antioxidant 3114,antioxidant 1010,antioxidant 330,antioxidant 1076,antioxidant 168)in pharmaceutical packaging plastic pellets and to inspect the content of antioxidants in pharmaceutical packaging plastic pellets in the market used by pharmaceutical packaging manufacturers.Methods: Using acetonitrile as the extraction solvent,HPLC was adopted for determination of antioxidants content in plastic pellets.The chromatographic column was Diamonsil C₁₈(150 mm×4.6 mm,5 μm).The mobile phase was acetonitrile and water with a gradient mode at the flow rate of 1.5,1.8 mL·mol^-1.The UV detection wavelength was set at 224 nm.Results: This method could separate and determine eight kinds of commonly used antioxidants quickly and effectively.The antioxidants showed good linear relationship in a certain concentration ranges and the recoveries met the requirement.The 25 kinds of plastic pellets from different sources were collected for the determination of their antioxidant content,and the results were gathered to facilitate the selection of raw material for packaging in the future.The determination results of antioxidant 245,antioxidant 1178,antioxidant 264,antioxidant 1010,antioxidant 330,antioxidant 1076 and antioxidant 168 were 0.012%-0.046%,0-0.016%,0.002%-0.012%、0.003%-0.086%,0.007%-0.081%,0.006%-0.057%,respectively.Conclusion: The method is simple,accurate,and can be used for the determination of 8 commonly used antioxidants in pharmaceutical packaging plastic pellets and quality control.

[1] 谢兰桂,汤龙,孙会敏,等.再生塑料及其检测技术研究进展[J].药物分析杂志,2010,30(10):1985 XIE LG,TANG L,SUN HM,et al.Review on recycled plastic and its detection technologies[J].Chin J Pharm Anal,2010,30(10):1985
[2] 朱碧君,胡红刚,孙会敏,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 ZHU BJ,HU HG,SUN HM,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
[3] 高欣宇,王硕.塑料抗氧剂的种类、现状及发展趋势[J].天津科技,2010(2):80 GAO XY,WANG S.Type,current status and prospect of plastic antioxidant[J].Tianjin Sci Technol,2010(2):80
[4] 霍秀敏,马玉楠,蒋煜.药品与包装容器系统相容性研究探讨[J].中国新药杂志,2012,22(19):2226 HUO XM,MA YN,JIANG Y.Commentary on compatibility of drug products and their container systems[J].Chin J New Drugs,2012,22(19):2226
[5] 张宇.药用丁基胶塞与药物相容性研究现状和展望[J].天津药学,2010,2(1):72 ZHANG Y.Current status and prospect of drug compatibility research on medicinal butyl rubber[J].Tianjin Pharm,2010,2(1):72
[6] 周健丘,梅丹.药品包装材料与药品质量和安全性的影响[J].药物不良反应杂志,2011,13(1):27 ZHOU JQ,MEI D.Influence of pharmaceutical packaging materials on quality and safety of medicines[J].Adv Drug React J,2011,13(1):27
[7] 赵霞.药用丁基胶塞与头孢曲松钠的相容性研究[D].北京:中国协和医科大学,2006 ZHAO X.Research on the Compatibility Between Medicinal Butyl Rubber and Ceftriaxone Sodium[D].Beijing:Peking Union Medical College.2006
[8] 许宗颖,刘兴兰,蒲小聪.HPLC法测定五层共挤输液用袋中抗氧剂1178的含量[J].中国药师,2015,18(5):876 XU ZY,LIU XL,PU XC.HPLC determination of antioxidant 1178 of five-layer co-extrusion bag[J].China Pharm,2015,18(5):876
[9] EP 9.0[S].2017:403
[10] 霍秀敏,马玉楠,蒋煜.直接接触注射剂的包装材料和容器的选择原则[J].中国临床药理学杂志,2012,156(10):797 HUO XM,MA YN,JIANG Y.Selection principle and evaluation key points of immediate contact packaging materials and containers for pharmaceutical injections[J].Chin J Clin Pharmacol,2012,156(10):797
[11] 郭春海,陈瑞春,马育松,等.食品接触材料聚乙烯和聚丙烯中9种抗氧化剂在食品模拟物中的迁移规律研究)[J].包装工程,2011,32(17):20 GUO CH,CHEN RC,MA YS,et al.Research for migration rule of 9kinds of antioxidants in food contact PE and PP film to food simulants[J].Pack Eng,2011,32(17):20
[12] 王正林,刘志刚,胡长鹰,等.聚烯烃抗氧1076和168在食用油中的迁移研究[J].包装工程,2007,28(6):1 WANG ZL,LIU ZG,HU CY,et al.Migration of polyolefin antioxidants irganox 1076 and irganox 168 in edible oils[J].Pack Eng,2007,28(6):1
[13] 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):160 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):160