B-297 Magnetic Bead-Based Automated Sample Preprocessing for LC-MS/MS-Based Therapeutic Drug Monitoring

Abstract Background Therapeutic Drug Monitoring (TDM) plays a crucial role in optimizing drug therapy and toxin testing. Traditional sample preparation techniques, such as protein precipitation, often encounter challenges, including low automation, matrix effects, and interference from large molecules, which can impact both accuracy and sensitivity. While immunoassays offer speed and sensitivity, they are limited in terms of drug versatility and may suffer from cross-reactivity. To address these limitations, magnetic bead-based automated sample preparation has emerged as a promising solution. This method facilitates drug extraction, purification, and minimizes matrix effects, making it ideal for complex biological matrices. With its high efficiency, broad compatibility with various drug types, and automation capabilities, magnetic bead-based preparation is well-suited for TDM applications in both clinical and pharmaceutical research, as well as toxin management. Methods Magnetic beads functionalized with silica materials were employed to selectively extract multiple target drugs from serum samples. This process was integrated into an automated system capable of processing up to 96 samples within 10 minutes. The high-throughput method eliminates the need for centrifugation and vortexing, reducing interference from phospholipids. Drug extraction efficiency and specificity were evaluated across a broad range of drug classes. The system was tested with various drugs, including antipsychotics, antidepressants, antiepileptics, analgesics, and others, demonstrating excellent extraction efficiency and sample purification. LC-MS/MS was used for precise quantification of the extracted drugs. Results The magnetic beads demonstrated high efficiency in extracting a wide range of therapeutic drugs from serum samples. The beads, with their unique surface structure, efficiently captured both non-polar and polar compounds, resulting in superior extraction performance compared to traditional protein precipitation. The method optimized extraction conditions, such as pH adjustments, and minimized interference from phospholipids, improving sensitivity and accuracy in therapeutic drug monitoring (TDM) applications. Conclusion Magnetic bead-based automated sample preparation offers a rapid, high-throughput solution for TDM. The method ensures efficient drug extraction, minimizes sample matrix interference, and improves the precision of drug quantification using LC-MS/MS. With reduced manual labor, shorter processing times, and enhanced sensitivity, this approach is ideal for clinical and pharmaceutical applications, providing a reliable and standardized tool for therapeutic drug monitoring across diverse drug classes.