GC-MS/HPLC法分析注射用头孢美唑钠丁基胶塞中有机成分及其迁移  

Analysis of Organic Components and Their Migration Studies in Butyl Rubber Clousures of Cefmetazole Sodium for Injection by GC-MS/HPLC

作　　者：张凤妹 陈丹丹 徐兵勇 梁键谋 刘珊 袁利佳 ZHANG Fengmei;CHEN Dandan;XU Bingyong;LIANG Jianmou;LIU Shan;YUAN Lijia(Zhejiang Institute for Food and Drug Control,Key Laboratory for Core Technology of Generic Drug Evaluation National Medical Product Administration&Key Laboratory of Drug Contacting Materials Quality Control of Zhejiang Province,Hangzhou 310052,China;Zhejiang University of Technology,Hangzhou 310014,China;Center for Drug Evaluation,NMPA,Beijing 100022,China)

机构地区：[1]浙江省食品药品检验研究院,国家药品监督管理局仿制药评价关键技术重点实验室&浙江省药品接触材料质量控制研究重点实验室,杭州310052 [2]浙江工业大学,杭州310014 [3]国家药品监督管理局药品审评中心,北京100022

出　　处：《医药导报》2023年第12期1819-1825,共7页Herald of Medicine

基　　金：2022年度浙江省药监局科技计划项目(2022019)。

摘　　要：目的考察注射用头孢美唑钠胶塞中有机成分及其向药物中的迁移,评价药用丁基胶塞与头孢美唑钠的相容性。方法采用气质联用色谱(GC-MS)法并利用美国国家标准技术研究院(NIST)谱库,鉴定了注射用头孢美唑钠丁基胶塞中及迁移入药品中挥发性成分的结构;建立HPLC法定量分析从丁基胶塞迁移入药品中的抗氧剂和硫化剂。结果通过GC-MS法鉴定胶塞中含有抗氧剂BHT、硅油等有机物成分;高效液相色谱(HPLC)法测定抗氧剂(168、264、330、1076、1010)和硫化剂均在0.5~100μg·mL^(-1)范围内与峰面积呈良好的线性关系;通过添加标准品回收实验,抗氧剂和硫化剂的平均回收率(低、中、高)均在90.0%~110.0%之间,对应的RSD(%)均小于2%(n=9)。注射用头孢美唑钠丁基胶塞中抗氧剂BHT、硅油等成分会迁移进入药品中,影响溶液的澄清度。结论GC-MS/HPLC法可作为药品包装材料(丁基胶塞)质量控制及药品相容性研究的有效方法,保障公众用药安全。Objective To investigate the organic components in cefmetazole sodium butyl rubber clousures for injection and their migration into drugs,and to evaluate the compatibility of pharmaceutical butyl rubber clousures with cefmetazole sodium.Methods The structures of volatile components in butyl rubber clousures of cefmetzole sodium for injection and those migrated into drugs were identified by GC/MS SCAN mode and National Institute of Standard and Technology(NIST)spectrum library.An HPLC method was established to quantitatively analyse the antioxidants and vulcanizing agents transferred from butyl rubber clousures into drugs.Results Organic compounds such as antioxidant BHT and silicone oil were identified by GC/MS.The HPLC was used to determine the peak area of antioxidant(168,264,330,1076,1010)and vulcanizing agent in the range of 0.5-100μg·mL^(-1) with good linear relationship with the peak area.The average recoveries(low,medium,and high)of antioxidant and vulcanizing agents ranged from 90.0%to 110.0%,and the corresponding RSD were all less than 2%(n=9).It was found that the antioxidant BHT and silicone oil in cefmetazole sodium butyl rubber clousures for injection would migrate into the drug and affect the clarity of the solution.Conclusion GC-MS/HPLC method can be used as an effective method for quality control of packing materials(butyl rubber clousures)and drug compatibility studies,so as to ensure the safety of drug use by the public.

关 键 词：注射用头孢美唑钠 丁基胶塞 硫化剂 抗氧剂 迁移 

分 类 号：R978.1[医药卫生—药品] R927.2[医药卫生—药学]