Electromembrane extraction and mass spectrometry for liver organoid drug metabolism studies

Abstract 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)...

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Published inbioRxiv
Main Authors Frøydis Sved Skottvoll, Hansen, Frederik, Harrison, Sean, Boger, Ida Sneis, Ago Mrsa, Magnus Saed Restan, Stein, Matthias, Lundanes, Elsa, Pedersen-Bjergaard, Stig, Aizenshtadt, Aleksandra, Krauss, Stefan, Sullivan, Gareth, Bogen, Inger Lise, Wilson, Steven Ray
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 04.12.2020
Subjects
Biomaterials
Capillary electrophoresis
Chromatography
Drug abuse
Drug development
Drug metabolism
Heroin
Liquid chromatography
Liver
Mass spectrometry
Mass spectroscopy
Metabolism
Metabolites
Organoids
Scientific imaging
Stem cells
Toxicity
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Summary:Abstract 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 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. Competing Interest Statement The authors have declared no competing interest. Footnotes * This version is extended in information for all parts of the manuscript. In addition, some new results and references are added.
DOI:10.1101/2020.05.15.095174