A New Workflow for Metals Analysis in Biopharmaceutical Samples of Complex Matrix Using an Automated Preparation System Coupled to ICP‐MS

ABSTRACT Accurate determination of both major and trace metals in biopharmaceutical materials is crucial for quality control, as fluctuations in metal concentrations can affect cell growth, manufacturing yield, and overall product quality. However, the complex matrices of many biopharmaceutical samples, particularly those with high saline content, pose significant challenges for metal detection by ICP‐MS due to severe matrix effects and spectral interferences. In addition, the preparation of multiple standards and diluted samples is often labor‐intensive and time‐consuming. This study introduces a novel workflow that overcomes the analytical challenges by eliminating biopharmaceutical matrices and preconcentrating trace metals. An automated sample preparation system, seaFAST, originally designed for seawater analysis, was employed for preparing biopharmaceutical materials. The samples pass through a chelation column, where metals of interest are preconcentrated and sample matrices are removed. Following optimization, the seaFAST system was successfully coupled with a triple quadrupole ICP‐MS for detecting metals in cell culture media and vaccine samples using both direct and preconcentration modes. The method demonstrated excellent linearity, accuracy, and precision. Compared to traditional techniques, this approach significantly improved detection limits for biopharmaceutical materials with complex matrices. Moreover, manual preparation of multiple calibration standards and sample dilutions was eliminated through autocalibration and autodilution features. This new workflow effectively removes complex matrix interferences while preconcentrating trace metals, achieving a higher level of automation for biopharmaceutical materials. This integrated system offers a valuable tool for metals analysis in this field.