DMetFinder: A novel mass spectrometry analysis tool for comprehensive drug metabolite detection

The study of drug metabolites is essential for evaluating safety and optimizing drug design. Recent classes of high-molecular-weight drugs, such as PROTACs and LYTACs, present challenges for traditional metabolite identification approaches due to their complex structures. To address these limitations, we developed Drug Metabolite Finder (DMetFinder), a novel mass spectrometry-based tool designed to enhance metabolite identification. DMetFinder employs cosine similarity algorithms to filter compounds with similar structures, minimizing the risk of overlooking metabolites with large fragment losses. It also efficiently detects multiply charged ions and incorporates isotope abundance and adduct ion scoring to refine identification accuracy. By calculating a total weighted score, DMetFinder reduces false positives associated with single-filter strategies. Experimental validation demonstrates that DMetFinder significantly improves the identification of metabolites from PROTACs, providing valuable insights for future drug development.