biostudies-literatureKim MKorean National Police AgencyMinistry of EducationKorea Customs ServiceKorean National Police University69-75https://www.ebi.ac.uk/biostudies/studies/S-EPMC12809649biostudies-literatureUnknown98(1)Feature-Based Molecular Networking (FBMN) on the Global Natural Products Social Molecular Networking (GNPS) platform offers a transformative framework for visualizing drug-drug interaction (DDI)-driven metabolic reprogramming that conventional analytical approaches fail to capture. Here, we demonstrate its application as a novel strategy to resolve complex metabolic alterations arising from DDI-induced toxicity. Using FBMN-integrated MS² mapping, we established a proof-of-concept workflow to elucidate large-scale metabolic transitions and pathway rewiring. As a model system, co-administration of methamphetamine (MA) and ethanol (EtOH)─a combination known to potentiate toxicity─was analyzed through liquid chromatography-quadrupole time-of-flight mass spectrometry. Merging MS<sup>Analytical chemistryGNPS Feature-Based Molecular Networking as a Tool to Visualize Metabolic Toxicity from Drug-Drug Interactions: A Case Study with Methamphetamine and Ethanol.PMC12809649RS-2023-00242428RS-2024-00406234Yoo SJLee SKim JHKim MfalseGNPS Feature-Based Molecular Networking as a Tool to Visualize Metabolic Toxicity from Drug-Drug Interactions: A Case Study with Methamphetamine and Ethanol.Feature-Based Molecular Networking (FBMN) on the Global Natural Products Social Molecular Networking (GNPS) platform offers a transformative framework for visualizing drug-drug interaction (DDI)-driven metabolic reprogramming that conventional analytical approaches fail to capture. Here, we demonstrate its application as a novel strategy to resolve complex metabolic alterations arising from DDI-induced toxicity. Using FBMN-integrated MS² mapping, we established a proof-of-concept workflow to elucidate large-scale metabolic transitions and pathway rewiring. As a model system, co-administration of methamphetamine (MA) and ethanol (EtOH)─a combination known to potentiate toxicity─was analyzed through liquid chromatography-quadrupole time-of-flight mass spectrometry. Merging MS<sup>2026-01-01T00:00:00Z2026 Jan2026-06-06T16:06:54.667Z2026-06-02T03:12:24.64ZS-EPMC128096494148119810.1021/acs.analchem.5c06388