Application of Analytical Quality by Design (AQbD) in Developing Robust Methods for Herbicide Analysis-A Case Study on Metribuzin

Analytical Quality by Design (AQbD) applies Quality by Design principles to analytical method development, aiming to design methods that are robust, well-understood, and life cycle managed. Herbicide residue analysis (monitoring active compounds and metabolites in formulations, food, soil, and water) presents challenges of trace-level detection, matrix complexity, and regulatory limits. Metribuzin — a widely used triazinone herbicide — has multiple analytical procedures reported (UV/vis spectrophotometry, HPLC-UV, LC– MS/MS, GC–MS/MS, electrochemical and sensorbased approaches). This review synthesizes AQbD theory and tools, surveys analytical methods for metribuzin, and proposes an AQbD-driven workflow tailored to herbicide analysis with practical examples from the literature. By combining Analytical Target Profile (ATP) definition, risk assessment, systematic Design of Experiments (DoE), method operable design region (MODR) determination, and control strategy, AQbD offers a structured path to methods that meet regulatory and environmental surveillance needs while improving robustness and transferability. The review highlights existing applications of DoE/optimization in metribuzin analysis, identifies gaps where AQbD could add value (e.g., multiresidue LC–MS workflows and metabolite quantification), and outlines a recommended AQbD case study plan for future thesis work on metribuzin analysis.