HPLC法同时测定药用卤化丁基胶塞中17种抗氧剂向注射用伏立康唑中的迁移  

Determination of migration of 17 antioxidants from pharmaceutical halogenated butyl rubber stopper to voriconazole for injection by HPLC

作　　者：张旭 傅萍 谢华 袁军 常艳波 ZHANG Xu;FU Ping;XIE Hua;YUAN Jun;CHANG Yan-bo(Sichuan Institute for Food and Drug Control,Chengdu 611731,China;Dechang People’s Hospital,Liangshan 615500,China)

机构地区：[1]四川省食品药品检验检测院,成都611731 [2]德昌县人民医院,凉山615500

出　　处：《药物分析杂志》2020年第8期1481-1489,共9页Chinese Journal of Pharmaceutical Analysis

基　　金：“重大新药创制”科技重大专项(2017ZX09101001)。

摘　　要：目的:建立药用卤化丁基胶塞中17种抗氧剂向注射用伏立康唑中迁移的检测方法。方法:采用InertSustain C18色谱柱(4.6 mm×250 mm,5μm),以0.02 mol·L^-1甲酸铵(甲酸调节pH至5.0)-甲醇为流动相,梯度洗脱,流速1.0 mL·min^-1,检测波长277 nm,柱温30℃,进样量10μL。结果:17种抗氧剂之间的分离度良好;抗氧剂1076、1010、1035、168、1520在1~16μg·m L^-1浓度范围内线性关系良好(r2=0.9999);其余抗氧剂在0.5~8.0μg·mL^-1浓度范围内线性关系良好(r2=0.9999)。方法精密度、重复性、回收率、稳定性均符合有关规定。4家企业12批次样品中共计检出10种抗氧剂发生迁移,分别为DBHQ、BHT-COOH、BHT-OH、BHT-CHO、DBP、BHT-Q、BHT、2246、1035、445。结论:该方法灵敏度高,操作简单,重复性好,可用于药用卤化丁基胶塞中17种抗氧剂向注射用伏立康唑中迁移量的测定。Objective:To establish an HPLC method for monitoring the migration of 17 antioxidants from pharmaceutical halogenated butyl rubber stopper to voriconazole for injection. Methods:HPLC was performed on an InertSustain C18 column(4.6 mm×250 mm,5 μm)with the mobile phase of 0.02 mol·L^-1 ammonium formate(adjusted to pH 5.0 with formic acid)-methanol(gradient elution). The flow rate was 1.0 mL·min^-1,the detection wavelength was 277 nm,the column temperature was maintained at 30 ℃ and the sample volume was 10 μL. Results:The resolutions between 17 antioxidants were great. The antioxidants(1076,1010,1035,168,1520) and the other antioxidants showed good linear relationship in the concentration range of 1-16 μg·mL^-1(r2=0.999 9)and 0.5-8.0 μg·m L^-1(r2=0.999 9),respectively. The precision,repeatability,recovery rate and stability were in line with the relevant requirements. A total of 10 kinds of antioxidants were detected in 12 batches of samples from 4 companies,which were DBHQ,BHT-COOH,BHT-OH,BHT-CHO,DBP,BHT-Q,BHT,2246,1035,445. Conclusions:The method is sensitive,rapid and accurate with good repeatability,which is used to determine the migration of 17 antioxidants from pharmaceutical halogenated butyl rubber stopper to voriconazole for injection.

关 键 词：胺类抗氧剂 酚类抗氧剂 亚磷酸酯类抗氧剂 注射用伏立康唑 药用卤化丁基胶塞 高效液相色谱法 

分 类 号：R917[医药卫生—药物分析学]