A validated UHPLC-MS/MS method for simultaneous quantification of 9 exocyclic DNA adducts induced by 8 aldehydes

Helena Alamil (1) , Mathilde Lechevrel (1) , Stéphanie Lagadu (1) , Laurence Galanti (2) , Zeina Dagher (3) , Raphaël Delépée (1)

1 ABTE - Aliments Bioprocédés Toxicologie Environnements
2 CHU UCL Namur
3 LU - Lebanese University [Beirut]

Human exposure to aldehydes is implicated in several diseases including cancer. These strong electrophilic compounds can react with nucleophilic sites in DNA to form reversible and irreversible modifications. These modifications, if not repaired, can contribute to pathogenesis. The aim of our study was to provide a mass spectrometry (MS)-based profiling method for identifying potential biomarkers of aldehydes exposure. We have developed and validated a highly sensitive method using ultra high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) for the simultaneous quantitation of 9 exocyclic DNA adducts derived from 8 main exogenous and endogenous aldehydes, namely formaldehyde, acetaldehyde, acrolein, crotonaldehyde, malondialdehyde, 4-hydroxy-2-nonenal, glyoxal and methylglyoxal. Finally, we applied the established method to quantify adducts in genomic DNA isolated from the blood of a smoker and a non-smoker blood samples in order to demonstrate its applicability.

Keywords: Adductomic; Aldehydes; Analytical method validation; Cancer; Exposure biomarkers; Oxidative stress; Ultrahigh performance liquid chromatography -electrospray ionization- tandem mass spectrometry

Domains: Molecular biology; Cancer; Health; Toxicology; Analytical chemistry

Helena Alamil, Mathilde Lechevrel, Stéphanie Lagadu, Laurence Galanti, Zeina Dagher, et al.. A validated UHPLC-MS/MS method for simultaneous quantification of 9 exocyclic DNA adducts induced by 8 aldehydes. Journal of Pharmaceutical and Biomedical Analysis, 2020, 179, pp.113007. ⟨10.1016/j.jpba.2019.113007⟩. ⟨hal-02461102⟩