电感耦合等离子体质谱(ICP-MS)法测定生物制药用一次性储液瓶中34种可提取无机元素

为建立同时测定生物制药用一次性储液瓶中34种可提取无机元素含量的方法，采用5种溶剂对样品分别提取1天、21天和70天，利用电感耦合等离子体质谱仪（ICP-MS）检测其中的元素含量，通过比较各检出元素的含量与人每日最大允许暴露量（PDE）进行风险评估。结果表明，该方法下各元素拟合曲线线性良好，相关系数≥0.999，不同提取溶剂中，方法的检出限为0.001-25.772 μg/L，相对标准偏差范围为0.2%-2.3%，低、中、高加标平均回收率在86.0%-115.7%之间。实际样品测定时，不同提取条件下可提取元素的含量在水和碱性溶液中较高，而随提取时间的增加趋势并不显著，各检出元素的含量均远低于其PDE值。该方法检出限低，线性良好，具有较高的准确度和精密度，可以满足生物制药用一次性储液瓶中多种可提取无机元素同时检测的需求。

Determination of 34 Extractable Inorganic Elements in Single-use Bottles used in Biopharmaceutical Manufacturing by ICP-MS

The objective of this work was to establish a method for simultaneous determination of 34 extractable elements in single-use bottles used in biopharmaceutical manufacturing. The samples were extracted by five solutions for 1, 21 and 70 days, respectively. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect element contents. Risk assessment was performed by comparing each element content with permitted daily exposure (PDE). The results showed that the liner correlation coefficients of the standard curves of each element were greater than 0.999. The limit of detection in different extraction solvents was 0.001-25.772 μg/L, and the relative standard deviation (RSD) was 0.2%-2.3%. The average recovery rate of low, medium and high spikes ranged from 86.0%-115.7%. In the actual sample determination, the element content of extractables in water and alkaline solution was higher, while the trend of element content increasing with extraction time was not significant. The content of each element was much lower than its PDE value. The method has low detection limit, good linearity, and high accuracy and precision, which could meet the needs of simultaneous detection of multiple elements in single-use bottles for biopharmaceuticals.