注射用去水卫矛醇与卤化丁基橡胶塞相容性研究中抗氧剂的含量测定

Determination of Antioxidant Content in the Study of Compatibility between Dianhydrodulcitol for Injection and Halogenated Butyl Rubber Stopper

目的:建立注射用去水卫矛醇直接接触药品内包材胶塞可能迁移入药品的抗氧剂1010、抗氧剂1076、抗氧剂3114、3,5-二叔丁基-羟基苯基丙酸(3,5-DTBHA)的反相高效液相色潽法含量测定方法并对其进行方法学验证。方法:采用C18色谱柱(2.7μm,100 mm×4.6 mm);流动相:0.1%磷酸水溶液:甲醇;流速1.0 mL·min^(-1);柱温40℃;检测波长为276 nm。结果:3,5-DTBHA、抗氧剂3114、抗氧剂1010、抗氧剂1076分别在0.99~5.93μg/mL、0.97~5.84μg/mL、0.97~5.84μg/mL、0.97~5.84μg/mL浓度范围内线性关系良好,相关系数都大于0.999。加标样品中的3,5-DTBHA、抗氧剂3114、抗氧剂1010、抗氧剂1076的平均回收率(n=9)分别为99.5%~103.9%,104.0%~105.9%、99.0%~105.3%及91.5%~96.9%。结论:该方法灵敏、快速,重复性好,操作简便,可用于注射用去水卫矛醇的直接接触内包装材料中添加的4种抗氧剂及其降解物的浸出物检测。

Objective: To establish a RP-HPLC method for the determination of antioxidant 1010, antioxidant 1076, antioxidant 3114,3,5-di-tert-butyl-hydroxyphenylpropionic acid(3,5-DTBHA) which may migrate into the drug in the case of direct contact with the rubber stopper of the drug inner packaging materials by dianhydrodulcitol for injection, and to verify its methodology. Method: Adopt C18chromatcolumn(2.7 μ m, 100 mm 4. 6 mm);mobile phase: 0.1% aqueous phosphate acid solution: methanol;flow rate 1.0 mL · min^(-1);column temperature 40℃;detection wavelength is 276 nm. Results: 3,5-DTBHA, antioxidant 3114, antioxidant 1010 and antioxidant 1076were well linear in the concentration range of 0.99 μg/mL to 5.93 μg/mL, 0.97 μg/mL to 5.84 μg/mL, 0.97 μg/mL to 5.84 μg/mL and 0.97μg/mL to 5.84 μg/mL, with a correlation coefficient greater than 0. 999. The average recovery rate(n = 9) of 3,5-DTBHA, antioxidant 3114, antioxidant 1010, and antioxidant 1076 in spiked samples were 99.5% to 103.9%, 104.0% to 105.9%, 99.0%to 105.3%, and 91.5%to 96.9%, respectively. Conclusion: The method is sensitive, rapid, reproducible and easy to operate. It can be used for the detection of extracts of four antioxidants and their degradation products added in the direct contact inner packaging materials of emarantol for injection.