Progress, applications, and challenges in high-throughput effect-directed analysis for toxicity driver identification...

Area of Science:

• Environmental Chemistry
• Toxicology
• Analytical Chemistry

Background:

• Increasing chemical production necessitates robust methods for assessing environmental and human health impacts.
• High-resolution mass spectrometry (HRMS) detects numerous compounds but identifying toxicity drivers in complex mixtures remains challenging.
• Effect-directed analysis (EDA) combines bioassays, fractionation, and chemical analysis to identify toxicity drivers.

Purpose of the Study:

• To provide an updated review of high-throughput effect-directed analysis (HT-EDA) methodologies.
• To discuss novel methods, tools, and computational approaches for accelerating EDA workflows.
• To identify current limitations in HT-EDA and propose solutions for improved environmental monitoring.

Main Methods:

• Review of existing literature on HT-EDA, including microfractionation, downscaled bioassays, and automation.
• Discussion of high-performance thin-layer chromatography (HPTLC) as an alternative to HPLC in HT-EDA.
• Exploration of computational prioritization tools and data processing workflows for HT-EDA.

Main Results:

• HT-EDA significantly accelerates the identification of toxicity drivers in complex environmental mixtures.
• Integration of automation, microplate-based fractionation, and advanced computational tools enhances HT-EDA efficiency.
• HPTLC presents a viable alternative for fractionation in HT-EDA, complementing microplate methods.

Conclusions:

• HT-EDA is crucial for overcoming the limitations of traditional EDA, enabling large-scale environmental monitoring.
• Further development of computational tools and novel methods like HPTLC integration will advance HT-EDA capabilities.
• This review highlights strategies to bridge the gap between current HT-EDA and its application in routine monitoring.