Currently, as of 2022, almost 200 million substances exist on the Chemical Abstracts Service (CAS) Registry and, of these, it is estimated that 350,000 chemical products have been licenced for manufacture and sale on a global level . As a consequence, identification and monitoring of large numbers of chemical compounds across multiple environmental compartments presents an enormous challenge. Recently, analytical approaches for non-target analysis (NTA) and suspect screening (SS) using liquid chromatography and high-resolution accurate mass spectrometry (LC-HRMS) have emerged and detect much larger numbers of compounds in a sample. However, NTA still presents multiple challenges, from ensuring detection of physico-chemically diverse compounds to reliably translating spectra of unknown substances into defined structures. Gaining comprehensive and confident knowledge of all sample components remains an aim still far to being fully achieved.