Liver organoids are emerging tools for precision drug development and toxicity screening. We demonstrate that electromembrane extraction (EME) based on electrophoresis across an oil membrane is suited for segregating selected organoid-derived drug metabolites prior to mass spectrometry (MS)-based measurements. EME allowed drugs and drug metabolites to be separated from cell medium components (albumin, etc.) that could interfere with subsequent measurements. Multiwell EME (parallel-EME) holding 100 μL solutions allowed for simple and repeatable monitoring of heroin phase I metabolism kinetics. Organoid parallel-EME extracts were compatible with ultrahigh-performance liquid chromatography (UHPLC) used to separate the analytes prior to detection. Taken together, liver organoids are well-matched with EME followed by MS-based measurements.

This perspective explores the feasibility of smart sampling with dried blood spots for the determination of proteins and peptides from human biomatrices using liquid chromatography coupled to mass spectrometry for clinical purposes. The focus is on innovative approaches to transform filter paper from a mere sample carrier to an active element in sample preparation, with the aim of reducing the need for extensive and intensive sample preparation in the conventional sense. Specifically, we discuss the use of modified cellulose to integrate sample preparation at an early stage of sample handling. The use of paper immobilized with either trypsin or monoclonal antibodies for protein digestion and affinity clean‐up is discussed as a potential benefit of starting sample preparation instantly at the moment of sampling to optimize time efficiency and enable faster analysis, diagnosis, and follow‐up of patients.

33Liver organoids (miniature, organ-like biomaterials derived from e.g. a patient´s stem 34 cells) are emerging tools for precision drug development and toxicity screening. We 35 demonstrate that electromembrane extraction (EME) is suited for collecting organoid-36 derived drug metabolites prior to mass spectrometry (MS)-based measurements. 37 EME, which is essentially electrophoresis across an oil membrane, allowed drugs 38 and drug metabolites to be separated from medium components (albumin, etc.) that 39 could interfere with subsequent measurements. Multi-well EME (100 µL solutions) 40 allowed for simple and repeatable monitoring of heroin metabolism kinetics. Organoid 41 EME extracts were compatible with ultrahigh-pressure liquid chromatography 42 (UHPLC) and capillary electrophoresis (CE), used to separate the analytes prior to 43 detection. These initial efforts show that organoids are well-matched with various 44 electrophoresis/chromatography techniques and MS measurements. 45 46 47