Challenges in effect-directed analysis with a focus on biological samples

• Effect-directed analysis (EDA) aims to identify compounds with adverse effects.
• Performing EDA of biota samples integrates bioavailability into EDA studies.
• Proper sampling and sample treatment of biota prior to EDA are challenging.
• Improvements in automated and high-throughput EDA are desired.
• EDA is promising tool for investigative monitoring and exposome research.

Effect-directed analysis (EDA), the combined use of bioassay-guided fractionation and analytical chemical techniques, enables detection of chemicals by their effects, facilitates identification of non-target compounds and transformation products with a certain toxic mode of action and assists in revealing mixture effects. To date, EDA has been restricted mainly to abiotic environmental compartments (e.g., sediment, water, and household dust) and has scarcely been applied to biotic compartments (e.g., tissue or homogenate of organisms, blood, and urine) due to difficulties in sample preparation of biological materials prior to bio/chemical analyses. EDA of biological samples is particularly suitable for: (i) identification of non-target compounds causing biological threat, while considering their bioavailability, bioaccumulation, and possible metabolization; or, (ii) indicating toxicity when the analyzed target compounds can only partly explain the measured effects. This overview discusses the importance, the challenges and the recent improvements in EDA with a focus on biota samples.