# Development of LC-MS/MS Database Based on 250 Potentially Highly Neuroactive Compounds and Their Metabolites

## TL;DR

This paper describes the development of an LC-MS/MS database for 250 neuroactive environmental chemicals and their metabolites to better study their impact on neurodevelopmental disorders.

## Contribution

The novel contribution is the creation of a database with 274 compounds, including 55 newly discovered metabolites, to support exposomic research on neuroactivity.

## Key findings

- The database includes 94 parent compounds and 182 metabolites, with 55 being newly discovered.
- 87% of the database annotations are at confidence levels 1–2, ensuring high reliability for future studies.
- The database enhances the ability to identify these compounds and their metabolites in biological samples.

## Abstract

Background: Environmental chemicals are hypothesized to contribute to the development of neurodevelopmental disorders; however, only a fraction of the thousands of chemicals in common commercial use have validated assays. We recently developed the Environmental NeuRoactIve Chemicals (ENRICH) list of 250 chemicals prioritized for further testing due to their high likelihood of neuroactivity and human exposure, as derived through analysis across eight neuroactivity, exposure, and detection databases. Measuring some of these compounds in human biological media remains challenging due to the lack of information regarding their metabolites and detection frequencies. Methods: We created an LC-MS/MS database based on the targets in the ENRICH list using S9 human liver fractions to metabolize compounds individually and in groups into newly and previously discovered phase I metabolites. Results: The final database consisted of 274 compounds with 94 parent compounds and 182 metabolites being featured. A total of 55 novel metabolites were discovered. The confidence of the compounds, which were annotated correctly within the database, was high, increasing the odds of positive identifications within future exposomic work. The confidence of the annotations fell between the levels 1–3, with levels one and two consisting of 87% of the database. Conclusions: The creation of this database creates the opportunity for future biological studies centered around the impact these compounds and their metabolites have on the brain and for a better understanding of neurodevelopmental disorders and their origins.