Simulating Collision-Induced Dissociation Tandem Mass Spectrometry (CID-MS/MS) for the Blood Exposome Database Using Quantum Chemistry Methods - A Pilot Study

A significant number of compounds in exposome databases
and chemical
inventories lack mass spectral data due to the nonavailability of
reference standards. To address this limitation, computational chemistry
methods can be utilized to extend mass spectral libraries for a set
of chemicals. In this pilot study, we employed quantum-chemistry-based
software QCxMS to generate collision-induced dissociation mass spectra
for 121 compounds from the Blood Exposome Database. We developed a
scalable computational framework that integrates QCxMS and additional
tools, utilizing a grid-based parameter selection strategy and defined
coverage criteria. Our approach systematically explored protomeric
isomers and applied predefined parameter combination sets sequentially
based on molecular structures. This workflow produced high-quality in silico spectra for 81 compounds that achieved entropy
similarity scores ≥700 and at least two matching fragment ions
against the NIST23 library, yielding 71% spectral coverage. These
results highlight the importance of optimizing simulation parameters
and accounting for protomeric diversity to enhance the spectral quality
and computational efficiency. This workflow provides a practical strategy
to add mass spectral data for most compounds in the Blood Exposome
Database at reasonable computational cost, supporting the spectral
library expansion for improved compound annotation in exposomics.