注射用艾司奥美拉唑钠丁基橡胶塞中抗氧剂BHT及其氧化产物迁移量的测定  

Determination of the migration quantity of antioxidant BHT and its oxidation product in butyl rubber stopper of esomeprazole sodium for injection

作　　者：薄晓文 沈永[1,2,3] 孟凯 亓晓庆 徐志洲 BO Xiao-wen;SHEN Yong;MENG Kai;QI Xiao-qing;XU Zhi-zhou(Shandong Quality Inspection Center for Medical Devices,Jinan 250101,China;NMPA Key Laboratory for Quality Control of Pharmaceutical Packaging,Jinan 250101,China;Shandong Key Laboratory of Biological Evaluation for Medical Devices,Jinan 250101,China)

机构地区：[1]山东省医疗器械产品质量检验中心,济南250101 [2]国家药品监督管理局药品包装材料质量控制重点实验室,济南250101 [3]山东省医疗器械生物学评价重点实验室,济南250101

出　　处：《药物分析杂志》2020年第10期1863-1869,共7页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立注射用艾司奥美拉唑钠与丁基橡胶塞相容性研究中抗氧剂2,6-二叔丁基对甲酚(BHT)及其氧化产物2,6-二(叔丁基)-4-羟基-4-甲基-2,5-环己二烯-1-酮(BHT-O)迁移量测定的气相色谱-质谱(GC-MS)分析方法。方法:采用DB-5MS色谱柱,柱温为程序升温(40℃保持2 min,以10℃·min-1升温至200℃,以20℃·min-1升温至280℃);离子源温度为230℃,MS四极杆温度为150℃,扫描范围为35~400amu。结果:BHT及BHT-O质量浓度分别在103~1 030 ng·mL-1和298.9~3 486 ng·mL-1范围内线性关系良好(r>0.998);精密度试验结果的RSD分别为1.6%和3.2%;回收率分别为99.4%~100.5%和94.0%~104.2%;3批样品在长期试验中的BHT及BHT-O迁移量分别为100.0~321.2 ng·mL-1和298.9~1 051.5 ng·mL-1,在加速试验中其迁移量分别为100.0~338.8 ng·mL-1和298.9~835.2 ng·mL-1。结论:所建立的方法准确可靠,可用于注射用艾司奥美拉唑钠中抗氧剂BHT及其氧化产物迁移量的测定。Objective:To develop a gas chromatography-mass spectrometry(GC-MS) method for the determination of the migration quantity of antioxidant 2,6-di-tert-butyl-4-methylphenol(BHT) and its oxidation product 2,6-di-tert-butyl-4-hydroxy-4-methyl-2,5-cyclohexadien-1-one(BHT-O) in the compatibility study ofesomeprazole sodium for injection with butyl rubber stopper.Methods:The determination was performed on DB-5MS column by temperature programming:maintained at 40℃for 2 min,and then raised to 200℃at the rate of 10℃·min-1,and raised to 280℃at the rate of 20℃·min-1.EI ion source was used with temperature of 230℃.The temperature of MS quadrupole was 150℃and the scanning range was 35-400 amu.Results:The linearity of BHT and BHT-O was good (r>0.998) in the range of 103-1 030 ng·mL-1 and 298.9-3 486 ng·mL-1,respectively.The RSDs of precision test were 1.6%and 3.2%,respectively.The respective recoveries ranged from 99.4%to 100.5% and 94.0% to 104.2%.The migration quantities of BHT and BHT-O for 3 batches of samples were 100.0-321.2 ng·mL-1 and 298.9-1 051.5 ng·mL-1 during the long-term test,and 100.0-338.8 ng·mL-1 and 298.9-835.2 ng·mL-1 during the accelerated test,respectively.Conclusion:The method is accurate and reliable,and can be used to determine the migration quantity of antioxidant BHT and its oxidation product in esomeprazole sodium (freeze-dried) for injection.

关 键 词：注射用艾司奥美拉唑钠 2 6-二叔丁基对甲酚(BHT) 2 6-二(叔丁基)-4-羟基-4-甲基-2 5-环己二烯-1-酮(BHT-O) 抗氧剂 氧化产物 丁基橡胶塞 迁移量 长期试验 加速试验 气相色谱-质谱联用法 

分 类 号：R917[医药卫生—药物分析学]