药用胶塞中抗氧化剂的测定及其向药品中的迁移研究

Determination of antioxidants in medicinal rubber stopper and study on its migration into drugs

目的建立测定常见的5种抗氧化剂的高效液相色谱法(HPLC)。方法采用十八烷基键合高纯度球状硅胶色谱柱,以乙腈-四氢呋喃-水(62∶30∶8)为流动相,流速为1.5 mL/min,柱温为35℃,检测波长为278 nm,进样体积为20μL。对该方法的系统适用性、线性范围、准确度、重复性、检出限、定量限、稳定性进行分析,同时应用该方法分析抗氧剂在BTXA中的迁移情况。结果各抗氧剂重复性相对标准偏差(RSD)均小于0.7%,分离度均大于1.5。抗氧剂含量与峰面积平均值呈线性相关(P<0.0001)。BTXA中抗氧剂回收率为95%~105%;胶塞中抗氧剂回收率为87%~109%。抗氧剂BHT、抗氧剂1010、抗氧剂330、抗氧剂1076、抗氧剂168的重复性RSD值分别为3.6%、3.4%、3.7%、4.3%、4.7%。胶塞中仅检出抗氧剂BHT,平均为0.0142%,抗氧剂BHT的重复性RSD为1.9%。不同抗氧剂检出限范围为3.1~16.5 ng,定量限范围为4.6~45.5 ng。抗氧剂BHT、抗氧剂1010、抗氧剂330、抗氧剂1076、抗氧剂168的峰面积RSD值分别为0.3%、0.5%、0.4%、0.6%、0.4%。BTXA中均未检出抗氧化剂。结论该研究建立的HPLC法具有操作简单、方法准确可靠且分析成本较低的优点,可用于BTXA与药用卤化丁基胶塞相容性研究的常规分析与质量评价。

Objective To establish a high performance liquid chromatography(HPLC)method for the determination of five common antioxidants.Methods Octadecyl bonded high-purity spherical silica gel chrom-atographic column was used,acetonitrile tetrahydrofuran water(62∶30∶8)was used as mobile phase,the flow rate was 1.5 mL/min,the column temperature was 35℃,the detection wavelength was 278 nm,and the injection volume was 20μL.The system applicability,linear range,accuracy,repeatability,detection limit,quantitative limit and stability of the method were analyzed.At the same time,the migration of the antioxidant in BTXA was analyzed by the method.Results The relative standard deviation(RSD)of the repeatability of each antioxidant was less than 0.7%and the resolution was greater than 1.5.There was a linear correlation between the antioxidant content and the average peak area(P<0.0001).The recovery rate of the antioxidant in BTXA was 95%-105%.The recovery rate of antioxidant in rubber stopper was 87%-109%.The repeat-ability RSD values of antioxidant BHT,antioxidant 1010,antioxidant 330,antioxidant 1076 and antioxidant 168 were 3.6%,3.4%,3.7%,4.3%and 4.7%,respectively.Only the antioxidant BHT was detected in the rubber stopper,with an average of 0.0142%,and the repeatability RSD of the antioxidant BHT was 1.9%.The detection limits of different antioxidants ranged from 3.1 to 16.5 ng,and the quantitative limits ranged from 4.6 to 45.5 ng.The RSD values of peak areas of antioxidant BHT,antioxidant 1010,antioxidant 330,an-tioxidant 1076 and antioxidant 168 were 0.3%,0.5%,0.4%,0.6%and 0.4%,respectively.No antioxidant was detected in BTXA.Conclusion The HPLC method established in this study has the advantages of simple operation,high accuracy and reliability,and low analysis cost.It can be used for routine analysis and quality evaluation of the compatibility between BTXA and pharmaceutical halogenated butyl rubber stopper.