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

Abstract

The chemical exposome consists of environmental exposures experienced throughout a lifetime but to date analytical approaches to investigate the plethora of low-abundance chemicals remain very limited. Liquid chromatography high-resolution mass spectrometry (HRMS) is commonly applied 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 cover a broader chemical space 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, a triple quadrupole (QQQ) and a high-resolution mass spectrometer (HRMS) with identical chromatography were utilized to determine the limits of quantitation (LOQ) of >100 xenobiotics and estrogenic hormones in pure solvent and human urine. Both instrumental platforms are currently applied in exposure assessment studies and were operated in their most frequently used acquisition mode (full scan for HRMS and multiple reaction monitoring for QQQ) to mimic typical applications. For HRMS analyses, the median LOQ was 0.9 and 1.2 ng/mL in solvent and urine, respectively, while 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 female volunteers were investigated. 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 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 comprehensive exposome-wide association studies (ExWAS).