Critical assessment of the chemical space covered by 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 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.

Critical Assessment of the Chemical Space Covered by LC–HRMS Non-Targeted Analysis

“…In this review, we estimated the coverage of the chemical space of environmental samples by investigating recent NTA studies. To evaluate the impact of the selected workflow parameters on the coverage of chemical space, we collected information on these parameters (e.g., the type of mass analyzer, data acquisition mode, ionization mode, and size of the database used) from the studies . The identified compounds were categorized into classes, and their relative frequency of occurrence was determined.…”

“…The search for relevant studies that met these criteria was completed on March 1, 2023, and resulted in the inclusion of 61 studies for this review. 46 Collection of Instrumental Parameters. To capture the impact of each step of the NTA workflow on the chemical space coverage, we extracted specific parameters that were used in the studies we reviewed.…”

“…Finally, review articles and studies that did not perform any identification were excluded, as they did not contribute any additional methods or identified compounds. The search for relevant studies that met these criteria was completed on March 1, 2023, and resulted in the inclusion of 61 studies for this review …”

“…The search for relevant studies that met these criteria was completed on March 1, 2023, and resulted in the inclusion of 61 studies for this review. 46 …”

“…Lastly, we gathered information about the scope of the studies. The collected parameters, along with a list of the publications used in this review, are publicly available through the link in ref ( 46 ).…”