Organ-Specific Screening for Protein Damage Using Magnetic Bead Bioreactors and LC–MS/MS

A new 96-well plate methodology for fast, enzyme-multiplexed screening for metabolite-protein adducts was developed. Magnetic beads coated with metabolic enzymes were used to make potentially reactive metabolites that can react with test protein in the wells, followed by sample workup in multiple 96-well filter plates for LC-MS/MS analysis. Incorporation of human microsomes from multiple organs and selected supersomes of single cytochrome P450...