Electromembrane extraction and mass spectrometry for liver organoid drug metabolism studies

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