Comparing the sensitivity of low- and high-resolution mass spectrometry for xenobiotic trace analysis: A exposome-type case study

The chemical exposome consists of all environmental exposures experienced throughout a lifetime. Liquid chromatography high-resolution mass spectrometry (HRMS) is common in untargeted exposome-wide analyses of xenobiotics in biological samples; however, human biomonitoring approaches usually utilize targeted low-resolution triple quadrupole (QQQ) mass spectrometry tailored to a small number of chemicals. HRMS can identify novel contaminants over a broad mass range but the detection of molecules from low-level exposure amidst a background of highly-abundant endogenous molecules has proven to be difficult. In this study, high- and low-resolution mass spectrometry with identical chromatography was utilized to determine the limits of quantitation (LOQ) of >100 xenobiotics and estrogenic hormones in pure solvent and human urine. For HRMS analyses, the median LOQ was 0.9 and 1.2 ng/mL in solvent and urine, respectively and for low-resolution QQQ measurements, the median LOQ was 0.1 and 0.2 ng/mL in solvent and urine, respectively. To evaluate the calculated LOQs in complex biological samples, spot urine samples from 24 Nigerian females were measured. The higher LOQ values for HRMS resulted in less quantified low-abundance analytes and decreased the number of compounds detected below the LOQ. Even at chronic low-dose exposure, such compounds might be relevant for human health because of a high individual toxicity or potential mixture effects. Nevertheless, HRMS enabled the additional screening for exposure to unexpected/unknown analytes, including emerging compounds and biotransformation products. Therefore, a synergy between high- and low-resolution mass spectrometry may currently be the best option to elucidate and quantify xenobiotics in exposome-wide association studies (ExWAS).