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

Abstract

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.