Title: Investigation of human microphysiological systems using mass spectrometry-based qualitative analysis combined with metabolomics
Abstract:
Prediction of drug metabolism, drug effects, and drug-drug interactions are mostly investigated in animals and need to be validated in human models. However, limited access to human tissues, especially those that have not been exposed to disease and drugs, has hampered these efforts. Over the past decade, development of microphysiological systems aiming to represent relevant human physiology and organ-specific functions has accelerated, but publications have utilized mostly simple methods of biochemical analysis. Herein, we investigated human microphysiological systems using mass spectrometry-based qualitative analysis combined with metabolomics. An in vitro model of human brain was developed; meanwhile, a sophisticated human multiorgan microphysiological system was established for the comprehensive study of tolcapone metabolite profiling and metabolomics. Twelve tolcapone metabolites were identified, three of which are newly reported. Untargeted metabolomics identified key biomarkers that were significantly changed in human brain in vitro model after tolcapone dosing, which were mainly associated with perturbation of tryptophan and phenylalanine metabolism, glycerophospholipid metabolism, energy metabolism, and aspartate metabolism. The strategy of integrating drug metabolism with metabolomics not only provides a powerful approach to identify drug metabolites and endogenous biomarkers, but also widens our insights into the metabolic pathways perturbed by drug treatment, which are important for the investigation of drug efficacy and toxicity in human brain.
Audience Take Away Notes:
- Mass spectrometry could be considered as a powerful tool for the study of human microphysiological systems.
- Novel bioanalytical approach is developed by the combination of mass spectrometry-based qualitative analysis and metabolomics.
- This strategy of combining drug metabolism, metabolomics, and cell engineering opens a new window for applying analytical chemical methods to evaluate human responses to xenobiotics and other insults.
