Electromembrane Extraction and Mass Spectrometry for Liver Organoid Drug Metabolism Studies

电膜萃取和质谱法用于肝类器官药物代谢研究

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作者:Frøydis Sved Skottvoll, Frederik André 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

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.

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