Untargeted profiling of pesticide metabolites by LC–HRMS: an exposomics tool for human exposure evaluation

Abstract

Human exposure to xenobiotics is usually estimated by indirect methods. Biological monitoring has emerged during the last decade to improve assessment of exposure. However, biomonitoring is still an analytical challenge, because the amounts of sample available are often very small yet analysis must be as thorough and sensitive as possible. The purpose of this work was to develop an untargeted "exposomics" approach by using ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS), which was applied to the characterization of pesticide metabolites in urine from pregnant women from a French epidemiological cohort. An upgradable list of pesticides commonly used on different crops, with their metabolites (more than 400 substances) was produced. Raw MS data were then processed to extract signals from these substances. Metabolites were identified by tandem mass spectrometry; putative identifications were validated by comparison with standards and metabolites generated by experiments on animals. Finally, signals of identified compounds were statistically analyzed by use of multivariate methods. This enabled discrimination of exposure groups, defined by indirect methods, on the basis of four metabolites from two fungicides (azoxystrobin, fenpropimorph) used in cereal production. This original approach applied to pesticide exposure can be extended to a variety of contaminant families for upstream evaluation of exposure from food and the environment.

Combining UHPLC and high-resolution MS: A viable approach for the analysis of complex samples?

“…There is increasing activity in non-targeted approaches [67,81,82]. However, the complexity of matrices, the difference among them, and the low concentration of potential residues make such approaches very difficult.…”

“…Working "without" a reference material is certainly a strength of HRMS, since full-scan data are available. Papers reporting UHPLC-HRMS-based multi-residue methods intended to screen, to quantify, and to confirm pesticides [64][65][66][67][68] and veterinary drugs [69][70][71][72][73][74] have been published.…”

Future perspectives in Orbitrap™-high-resolution mass spectrometry in food analysis: a review

“…Although the data is occasionally used for risk assessment, there has been far less work on direct measurement of human exposure than other contaminant areas. It is therefore of interest that Jamin et al, (2014) have analysed human urine samples by dilution with mobile phase and direct injection into an UHPLC-HRMS system. A list of 425 compounds (i.e.…”

“…Twenty-four metabolites were putatively characterised among the 128 compounds detected in the raw data generated in the negative-ionisation mode, whilst only five compounds were putatively characterised under positive-ionisation conditions. Based on a statistical model generated by untargeted biomonitoring of 40 human subjects, exposure could be characterised on the basis of four metabolites of two fungicides, azoxystrobin and fenpropimorph, classically used as pesticides for treatment of cereal crops (Jamin et al, 2014).…”

Neonicotinoids and their Metabolites in Human Biomonitoring: A Review

“…It is foreseen that this approach can become a useful vehicle in forensic laboratories, which investigate human poisoning incidents with NNDs. Jamin et al (2014) published a cuttingedge work, in an untargeted profi ling of pesticide metabolites in urine from pregnant women from a French epidemiological cohort. To carry out such profi ling, the authors generated a pesticide metabolite list based on the likelihood of pesticide use in the study area.…”