Abstract

MALDI-TOF mass spectrometry has become a powerful tool for high-throughput screening (HTS) approaches in drug discovery, overcoming the shortcomings of conventional fluorescence label-based technologies. Most of the MALDI-TOF-based HTS approaches have focused on in vitro assays with simple readouts, and have been limited mainly to peptide/protein-centric activity assays. Although phenotypic cellular assays using MALDI-TOF MS are possible using higher molecular masses, the capability of MALDI-TOF to detect compounds in the low mass range is generally considered limited due to interference peaks brought by the matrix. Metabolomics-based drug discovery presents therefore an exciting challenge for MS analysis as the system becomes inherently more complex. Herein, we apply this technology for cellular assays, using primary human small airway epithelial cells, specifically to detect metabolites and lipids in a comprehensive, untargeted, and unbiased HTS approach for drug discovery in idiopathic pulmonary fibrosis.