Electromembrane Extraction and Mass Spectrometry for Liver Organoid Drug Metabolism Studies.

Affiliation

Skottvoll FS(1)(2), Hansen FA(3), Harrison S(2), Boger IS(1)(2), Mrsa A(1)(2), Restan MS(3), Stein M(4), Lundanes E(1), Pedersen-Bjergaard S(3)(5), Aizenshtadt A(2), Krauss S(2)(6), Sullivan G(2)(7), Bogen IL(8)(9), Wilson SR(1)(2).
Author information:
(1)Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, NO-0315 Oslo, Norway.
(2)Hybrid Technology Hub-Centre of Excellence, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, P.O. Box 1112, Blindern, NO-0317 Oslo, Norway.
(3)Department of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, NO-0316 Oslo, Norway.
(4)Institute of Medicinal and Pharmaceutical Chemistry, TU Braunschweig, Beethovenstr. 55, DE-38106 Braunschweig, Germany.
(5)Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
(6)Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 1110, Blindern, 0317, Oslo, Norway.
(7)Department of Pediatric Research, Oslo University Hospital and University of Oslo, P.O. Box 1112, Blindern, 0317 Oslo, Norway.
(8)Section for Drug Abuse Research, Department of Forensic Sciences, Oslo University Hospital, P.O. Box 4950, Nydalen, NO-0424 Oslo, Norway.
(9)Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, P.O. Box 1103, Blindern, NO-0317 Oslo, Norway.

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. 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.