From Target–Nontarget to Nontarget Screening: A Review on Screening Methods for Organic Pollutants Based on High-Resolution Mass Spectrometry

Although certain substances exist in the environment at trace concentrations, their ecological risks remain significant, making nontarget screening (NTS) one of the most important topics in the fields of environmental and analytical chemistry today. In recent years, with the development of high-resolution mass spectrometry (HRMS), the higher precision and accuracy have provided mass spectrometry (MS) characteristics with deeper application significance, offering new perspectives for NTS. This review briefly introduces the principles and methodologies of different MS characteristics and summarizes emerging advancements in screening strategies based on these characteristics. We innovatively propose a target-nontarget to nontarget screening workflow, which links different MS characteristics to achieve comprehensive NTS. This workflow prioritizes the currently applied MS characteristics, aiming to integrate various analytical steps to expand the screening coverage while maintaining reliability. The prioritization includes 1) mass defect (MD) analysis, 2) isotope patterns, 3) characteristic fragments, 4) construction of MS characteristics through chemical reactions, and 5) intermolecular connectivity MS characteristics mining. Subsequently, we provided an overview of the mining and prediction of MS characteristics based on machine learning. Finally, we evaluated the challenges of transitioning from target-nontarget to nontarget workflows and proposed future perspectives for NTS.