AQbD-Driven Method Development for Magnetic Nanoparticle Extraction and HPLC Analysis: A Comprehensive Review

The integration of analytical quality by design (AQbD) principles into analytical method development has revolutionized precision, robustness and regulatory compliance in the pharmaceutical and environmental sciences. This review explores the AQbD-driven optimization of magnetic nanoparticle (MNP) extraction coupled with high-performance liquid chromatography (HPLC) for enhanced analyte separation and quantification. The study outlines the systematic application of AQbD, including risk assessment, design of experiments (DoE) and control strategies, to optimize MNP extraction efficiency and chromatographic performance. Key aspects such as critical material attributes (CMAs), critical process parameters (CPPs) and critical quality attributes (CQAs) are identified to ensure method robustness and reproducibility. Furthermore, the article highlights the broad applicability of AQbD-based MNP-HPLC methods in pharmaceutical quality control, environmental monitoring and food safety analysis, especially after the advancement in magnetic nanoparticles application in different fields. Challenges associated with AQbD implementation in nanoparticle-based analytical techniques are also examined in pharmaceutical and environmental applications, alongside emerging trends such as computational modeling, artificial intelligence (AI)-driven optimization which is the most impactful for MNP-HPLC and automated method development. This review presents basic information from the 2008 UpToDate on the use of magnetic nanoparticles, while the application of AQbD in this context is relatively recent, having become widespread primarily after 2020.