HPLC法测定胶塞中抗氧剂1076向米卡芬净钠注射液中的迁移

目的：建立检测胶塞中抗氧剂1076向注射用米卡芬净钠药液中迁移量的监测方法。方法：采用以二乙烯基苯聚合物为填料的固相萃取小柱（HLB 200 mg/6 mL，30PK），用二氯甲烷：无水乙醇（2：3）5 mL进行洗脱。采用 XTerra C₁₈色谱柱（4.6 mm×150 mm，5 μm）；流动相：甲醇-水（98：2），流速1.0 mL·min^-1；柱温37 ℃；检测波长277 nm；进样量：20 μL。结果：抗氧剂1076在浓度为1~100 μg·mL^-1的范围内结果呈线性，线性关系良好（r=0.999 9），平均加样回收率为98.1 %，RSD为1.0 %（n=9）。精密度、稳定性、重复性均符合有关规定。各批号样品及在温度40 ℃，相对湿度75 %的环境中经过6个月高温度高相对湿度加速试验的样品中均未检测出抗氧剂1076。结论：该方法灵敏、快速、准确、重复性好，经方法学验证，可用于胶塞中抗氧剂1076向注射用米卡芬净钠药液中迁移量的监测。

Objective: To establish a HPLC method for moritoring the migration of antioxidant 1076 from rubber stopper to micafungin sodium injection. Method: Using the method of solid phase extraction column, packing with 2-Propenoic acid polymer with diethenylbenzene(HLB 200 mg/6 mL, 30 PK), and 5 mL of dichloromethane to ethanol(2:3)was 5 mL to elute. XTerra C₁₈ column(4.6 mm×250 mm, 5 μm)was used with methyl alcohol-water(98:2)as flow phase. The flow rate was 1.0 mL·min^-1, the column temperature was 37 ℃, the detection wavelength was 277 nm and the sample volume was 20 μL. Result: Antioxidant 1076 showed good linear relationship in range of 1-100 μg·mL^-1(r=0.999 9). The average recovery was 98.1%, and RSD was 1.0%(n=9). Precision, stability, repeatability are in line with the relevant provisions. Antioxidant 1076 was not detected in each batch of samples, micluding the samples after six months of high temperature and high relative humidity accelerated test at the temperature of 40 ℃ and the humidity 75% were not detected in antioxidant 1076. Conclusion: The method is sensitive, rapid and accurate with good repeatability, which can be used to determine the migration of antioxidant 1076 from rubber stopper to micafungin sodium injection.