A Novel Chemical-Space-Dependent Strategy for Compound Selection in Non-target LC-HRMS Method Development Using Physicochemical and Structural Data.

ABSTRACT: The virtual chemical space of substances, including emerging contaminants relevant to the environment and exposome, is rapidly expanding. Non-targeted analysis (NTA) by liquid chromatography-high-resolution mass spectrometry (LC-HRMS) is useful in measuring broad chemical space regions. Internal standards are typically used to optimize the selectivity and sensitivity of NTA LC-HRMS methods, assuming a linear relationship between structure and behavior across all analytes. However, this assumption fails for large, heterogeneous chemical spaces, narrowing measurable coverage to structurally similar compounds. We present a data-driven strategy for unbiased sampling of candidate structures for NTA LC-HRMS method development from extensive chemical spaces, such as the U.S. EPA's CompTox (>1 mil

SUBMITTER: Renai L 

PROVIDER: S-EPMC12424467 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature