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Electromembrane extraction and mass spectrometry for liver organoid drug metabolism studies

By Froydis Sved Skottvoll, Frederik Hansen, Sean Harrison, Ida Caroline Sneis Boger, Ago Mrsa, Magnus Saad Restan, Matthias Stein, Elsa Lundanes, Stig Pedersen-Bjergaard, Aleksandra Aizenshtadt, Stefan Krauss, Gareth Sullivan, Inger Lise Bogen, Steven Ray Wilson

Posted 16 May 2020
bioRxiv DOI: 10.1101/2020.05.15.095174

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. Multi-well EME (Parallel-EME) holding 100 microliter 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.

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