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Electromembrane extraction and mass spectrometry for liver organoid drug metabolism studies

Frøydis Sved Skottvoll, Frederik Hansen, Sean Harrison, Ida Sneis Boger, Ago Mrsa, Magnus Saed Restan, Matthias Stein, Elsa Lundanes, Stig Pedersen-Bjergaard, Aleksandra Aizenshtadt, Stefan Krauss, View ORCID ProfileGareth Sullivan, Inger Lise Bogen, View ORCID ProfileSteven Ray Wilson
doi: https://doi.org/10.1101/2020.05.15.095174
Frøydis Sved Skottvoll
aDepartment of Chemistry, University of Oslo, P.O. Box 1033, Blindern, NO-0315 Oslo, Norway
bHybrid 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
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Frederik Hansen
cDepartment of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, NO-0316 Oslo, Norway
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Sean Harrison
bHybrid 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
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Ida Sneis Boger
aDepartment of Chemistry, University of Oslo, P.O. Box 1033, Blindern, NO-0315 Oslo, Norway
bHybrid 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
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Ago Mrsa
aDepartment of Chemistry, University of Oslo, P.O. Box 1033, Blindern, NO-0315 Oslo, Norway
bHybrid 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
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Magnus Saed Restan
cDepartment of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, NO-0316 Oslo, Norway
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Matthias Stein
dInstitute of Medicinal and Pharmaceutical Chemistry, TU Braunschweig, Beethovenstr. 55, DE-38106 Braunschweig, Germany
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Elsa Lundanes
aDepartment of Chemistry, University of Oslo, P.O. Box 1033, Blindern, NO-0315 Oslo, Norway
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Stig Pedersen-Bjergaard
cDepartment of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, NO-0316 Oslo, Norway
eDepartment of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
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Aleksandra Aizenshtadt
bHybrid 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
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Stefan Krauss
bHybrid 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
iDepartment of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 1110 Blindern, 0317, Oslo, Norway
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Gareth Sullivan
bHybrid 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
fDepartment of Pediatric Research, Oslo University Hospital and University of Oslo, PO Box 1112 Blindern, 0317 Oslo, Norway
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Inger Lise Bogen
gSection for Drug Abuse Research, Department of Forensic Sciences, Oslo University Hospital, P.O. Box 4950 Nydalen, NO-0424 Oslo, Norway
hInstitute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, P.O. Box 1103 Blindern, NO-0317 Oslo, Norway
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Steven Ray Wilson
aDepartment of Chemistry, University of Oslo, P.O. Box 1033, Blindern, NO-0315 Oslo, Norway
bHybrid 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
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  • For correspondence: stevenw@kjemi.uio.no
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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.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted December 04, 2020.
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Electromembrane extraction and mass spectrometry for liver organoid drug metabolism studies
Frøydis Sved Skottvoll, Frederik Hansen, Sean Harrison, Ida Sneis Boger, Ago Mrsa, Magnus Saed Restan, Matthias Stein, Elsa Lundanes, Stig Pedersen-Bjergaard, Aleksandra Aizenshtadt, Stefan Krauss, Gareth Sullivan, Inger Lise Bogen, Steven Ray Wilson
bioRxiv 2020.05.15.095174; doi: https://doi.org/10.1101/2020.05.15.095174
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Electromembrane extraction and mass spectrometry for liver organoid drug metabolism studies
Frøydis Sved Skottvoll, Frederik Hansen, Sean Harrison, Ida Sneis Boger, Ago Mrsa, Magnus Saed Restan, Matthias Stein, Elsa Lundanes, Stig Pedersen-Bjergaard, Aleksandra Aizenshtadt, Stefan Krauss, Gareth Sullivan, Inger Lise Bogen, Steven Ray Wilson
bioRxiv 2020.05.15.095174; doi: https://doi.org/10.1101/2020.05.15.095174

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