Critical assessment of covered chemical space with LC-HRMS non-targeted analysis

Abstract

Non-targeted analysis (NTA) has emerged as a valuable approach for comprehensive monitoring of chemicals of emerging concern (CECs) in the exposome. The NTA approach, theoretically, is able to identify compounds with diverse physicochemical properties and sources. Non-targeted analysis methods, even though generic and wide scoping, have been shown to have limitations in terms of their coverage of the chemical space, as the number of the identified chemicals in each sample is very low (e.g. < 5%). Investigating the chemical space covered by each NTA assay is crucial for understanding the limitations and challenges associated with the workflow from experimental methods to the data acquisition and data processing. In this review, we examined recent NTA studies published between 2017 and 2023 that employed liquid chromatography-high resolution mass spectrometry. The parameters used in each study were documented and reported chemicals at the confidence level 1 and 2 were retrieved. The chosen experimental setups and the quality of reporting were critically evaluated and discussed. The findings revealed that only around 2% of the estimated chemical space (i.e. Norman SusDat) was covered by the NTA studies investigated. Little to no trend was found between the experimental setup and the observed coverage, due to the generic and wide scope of NTA studies. The limited coverage of chemical space by the NTA studies highlights the necessity for a more comprehensive approach in experimental and data processing setups to enable the exploration of a broader range of chemical space, with the ultimate goal of protecting human and environmental health. Recommendations to further explore a wider range of the chemical space were given.