HPLC测定卤化丁基胶塞中的抗氧剂在氨甲环酸注射剂中的迁移量

Migration of antioxidant from pharmaceutical halogenated butyl rubber stopper to tranexamic acid injection determined by HPLC

目的建立药用卤化丁基胶塞中11种抗氧剂向氨甲环酸注射剂中迁移的检测方法。方法采用Waters Symmetry C_(18)色谱柱(250 mm×4.6 mm,5μm),以乙腈(A)-甲醇(B)^(-1)%乙酸(C)为流动相,梯度洗脱,流速1.0 mL·min^(-1),检测波长277 nm,柱温35℃,进样量10μL。结果11种抗氧剂之间分离度良好,各组分在1.6~80μg·mL^(-1)与峰面积的线性良好,r2>0.995。样品的加标回收率为90.7%~107.4%,方法的重复性良好。6家企业共15批次样品,包括高温影响因素破坏样品均只检出BHT-COOH,其余抗氧剂均小于药品方法的检测限。结论所建方法灵敏度高、重复性好,可用于药用卤化丁基胶塞中11种抗氧剂向氨甲环酸注射剂中迁移量的测定。

OBJECTIVE To establish a method for the determination of 11 antioxidants in tranexamic acid injection which could migrate from pharmaceutical halogenated butyl rubber stopper.METHODS SHPLC was performed on Waters Symmetry C_(18)(250 mm×4.6 mm,5μm)column with acetonitrile(A)-methanol(B)-1%acetic acid solution(C)as the mobile phase with gradient elution at the flow rate of 1.0 mL·min^(-1).The detection wavelength was 277 nm and the column temperature was 35℃.The sample volume was 10μL.RESULTS The resolution of the 11 antioxidants was great,and all antioxidants showed good linear relationship in the concentration range of 1.6-80μg·mL^(-1)(r^(2)>0.9950).The recoveries of the samples were 90.7%-107.4%,and the reproducibility of the method was good.A total of 15 batches of samples from 6 companies,including samples damaged by high temperature factors,only BHT-COOH was detected,and other antioxidants were all lower than the detection limit of drug methods.CONCLUSION The method has high sensitivity and good repeatability,can be used for the determination of the migration amount of 1l antioxidants from pharmaceutical halogenated butyl rubber stopper to tranexamic acid injection.