Direct Electromembrane Extraction‐Based Mass Spectrometry: A Tool for Studying Drug Metabolism Properties of Liver Organoids

Abstract

AbstractThis work introduces a strategy for organoid analysis ‐ direct Electromembrane Extraction based Mass Spectrometry (dEME‐MS) – for coupling liver organoids with mass spectrometry (MS). dEME‐MS comprises electrophoresis of selected small molecules from a culture chamber across an oil membrane, and to a MS compatible solution. This enables clean micro‐extraction of drugs and their metabolites as produced in the liver organoids to capillary liquid chromatography‐mass spectrometry. Applying dEME‐MS, proof‐of‐concept of directly measuring methadone metabolism is demonstrated on adult liver organoids. With 50 liver organoids and 1 μM methadone, methadone metabolism was monitored from 0 to 24 hours (11 time points). All analytes had <0.4 % variance in retention times with >100 measurements. dEME‐MS is capable of automated and selective monitoring of drug metabolism in liver organoids, and could serve as a valuable tool for automated drug discovery efforts.