注射用泮托拉唑钠与组合包材相容性试验中元素杂质迁移研究

Research on Element Impurity Migration in the Compatibility Test of Pantoprazole Sodium for Injection with Combination Packaging Materials and Container

目的建立注射用泮托拉唑钠与中性硼硅玻璃管制注射剂瓶-覆膜塞组合包材相容性的电感耦合等离子体质谱(ICP-MS)实验方法。方法通过提取试验、模拟加速试验条件以及长期试验条件下的迁移实验,考察注射用泮托拉唑钠在不同时间下元素杂质的变化,对侵蚀后的模拟溶液进行分析,预测中硼管制瓶内表面脱片的倾向,并对其迁移量进行安全性评价。结果ICP-MS法测定各元素的线性关系良好,相关系数r均大于0.9990,定量限小于其相应限度10%。回收率为97.5%~108.8%。提取实验中,各样品中检出较高的元素为Si、B、Al,但均低于安全限度,其他元素的检出量较小,甚至低于检出限。在加速条件6、12个月和长期条件6、12个月下,包装材料中各种添加成分的元素杂质检测结果均低于分析评价阈值(AET)。结论该方法能有效测定样品中各杂质元素的含量,并揭示其迁移趋势。组合包材组件与注射用泮托拉唑钠的相容性良好,产品的安全性符合要求,为选择中硼管制瓶-覆膜塞作为内包材提供了科学依据。

OBJECTIVE To establish an experimental method using ICP-MS to study the compatibility between pantoprazole sodium for injection and neutral borosilicate glass injection bottle-coated stopper composite packaging materials.METHODS By conducting extraction experiments,simulated acceleration experiments,and migration experiments under long-term experimental conditions,the changes in elemental impurities of pantoprazole sodium for injection at different times were investigated.The simulated solution after erosion was analyzed to predict the tendency of detachment on the inner surface of boron tube bottles,and its migration amount was evaluated for safety.RESULTS The linear relationship of each element by ICP-MS method was good,and the correlation coefficient(r)was greater than 0.9990.The quantitative limit was less than its corresponding limit of 10%.The average recovery rate was 97.5%-108.8%.In the extraction experiment,the elements with higher detected level in each sample were Si,B,and Al,but all were below the safety limits.The detected levels of other elements were relatively low,even below the detection limits.Under intermediate and long-term conditions of 6 and 12 months,the detection results of elemental impurities in various added components in the packaging materials were all lower than the AET values.CONCLUSION This method can effectively determine the content of various impurity elements in the sample and reveal their migration trends.The compatibility between the composite packaging components and pantoprazole sodium for injection is good,and the safety of the product meets the requirements.It provided a scientific basis for selecting boron tube bottle and film-covered stopper as the inner packaging material.