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

•A set of 9 DNA adducts formed from 8 aldehydes were analysed by UHPLC-ESI-MS/MS.•The method was developed by using isotope dilution quantification with matrix extracted calibrators and QCs.•The method was fully validated following the EMA and FDA guidelines.•The method was applied to a smoker and a non-smoker Human samples. 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.