摘要
目的建立高效液相色谱法(HPLC)同时测定药用卤化丁基橡胶塞中8种抗氧剂可提取量及其在冻干人用狂犬病疫苗中迁移量的方法,为橡胶类药包材研究和质量控制标准的修订提供参考,有效保障药品安全。方法以十八烷基键合硅胶为填充剂(Waters XBridge C18色谱柱,4.6 mm×250 mm,5μm),以0.1%甲酸水溶液为流动相A,以体积分数0.1%甲酸甲醇溶液为流动相B,梯度洗脱(0.0~10.0 min,30%A→20%A;10.0~17.0 min,20%A;17.0~19.0 min,20%→1%A;19.0~37.5 min,1%A;37.5~39.0 min,1%→30%A;39.0~42.0 min,30%A);流速1.2 mL·min^(-1);柱温:30℃;检测波长277 nm。结果8种抗氧剂在10~500μg·mL^(-1)内呈良好的线性关系(r>0.9998);精密度试验的RSD为0.2%~2.4%;稳定性试验的RSD为1.3%~3.7%;提取回收率为85.7%~98.1%;迁移回收率为97.7%~99.8%。6家企业8批次药用胶塞样品中共计检出2种抗氧剂,其迁移样品中均未检出抗氧剂。结论本方法操作简单,稳定准确,灵敏度高,经方法学验证,可用于药用卤化丁基橡胶塞中抗氧剂可提取量及其在冻干人用狂犬病疫苗中的迁移量的测定。
OBJECTIVE To establish an HPLC method for simultaneous determination of eight antioxidants from pharmaceutical halogenated butyl rubber stoppers and their migration in freeze-dried rabies vaccines for human use,to provide reference for the research and quality control standards of rubber packaging materials and ensure drug safety.METHODS The analysis was carried out on Waters XBridge C18 column(4.6 mm×250 mm,5μm),using mobile phase consisting of 0.1% formic acid solution(A)-0.1% formic acid methanol solution(B)eluted by a gradient program(0.0-10.0 min,30%A→20%A;10.0-17.0 min,20%A;17.0-19.0 min,20%→1%A;19.0-37.5 min,1%A;37.5-39.0 min,1%→30%A;39.0-42.0 min,30%A)at a flow rate of 1.2 mL·min^(-1) at 30℃,the detection wavelength was set at 277 nm.RESULTS The linear relationships of the eight antioxidants were good in the concentration range of 10-500μg·mL-1(R>0.9998).The relative standard deviation of precision was 0.2%-2.4%,the relative standard deviation of stability was 1.3%-3.7%,the recovery rates of extraction were 85.7%-98.1%,and the recovery rates of migration were 97.7%-99.8%.Among the eight batches of samples from six companies,two antioxidants were detected in some pharmaceutical halogenated butyl rubber stopper samples,while no antioxidant was found in migration.CONCLUSION The method is sensitive,rapid,and accurate,which can be used to determine the extractable amounts of eight antioxidants in halogenated butyl rubber stoppers and their migration in freeze-dried rabies vaccines for human use.
作者
贾菲菲
程佳美
韩小旭
赵霞
杨会英
JIA Feifei;CHENG Jiamei;HAN Xiaoxu;ZHAO Xia;YANG Huiying(National Institutes for Food and Drug Control,Beijing 100050,China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2023年第23期2127-2132,共6页
Chinese Pharmaceutical Journal
基金
中国食品药品检定研究院中青年发展研究基金项目资助(2023C7)。
关键词
药用卤化丁基橡胶塞
冻干人用狂犬病疫苗
抗氧剂
可提取量
迁移量
halogenated butyl rubber stopper
freeze-dried rabies vaccine for human use
antioxidant
extraction amount
migration amount
