Even though these are possible structures, not all of them are likely to be present in the human and environmental exposome. When evaluating the exposome, the main difficulty is that the contents of the samples taken are unknown prior to analysis and may comprise of thousands of both known and unknown constituents, particularly for small molecules (i.e., molecular weight ≤ 1000 Da). A frequently used approach for analyzing such samples is non-targeted analysis (NTA) via liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS), for which a reversed phase (RP) LC selectivity is often used. However, it is not yet known what part of the chemical space is covered by RPLC. The knowledge of the covered subspace also contains crucial information on chemicals that might not be visible in the final data even though they were present in the sample. Knowing what is separable with RPLC can have an improved outcome for both NTA and suspect screening. For NTA, the aim is to identify as much as possible of the potentially thousands of chemicals present in samples coming from, for example, biological or environmental backgrounds. Eliminating the potential candidates that fall outside of the chemical subspace of the selectivity (e.g., RPLC), reduces the number of false positive identifications.