An integrated workflow for combined organic and inorganic chemical exposome analysis

Humans are exposed to a multitude of non-genetic factors throughout their lives, all of which are encompassed in the concept of the exposome. To assess its chemical component, combinations of complementary analytical techniques are needed for broad chemical space coverage. However, approaches for combined organic and inorganic analysis remain scarce and are further constrained by limited sample availability (e.g., in historical biobanks or preterm infants), as individual techniques require different sample preparation workflows. Therefore, we developed and evaluated an approach to combine sample preparation and analysis of organic and inorganic constituents of the exposome from a single low-volume sample aliquot (50 μL of blood or 50 mg of tissue). Liquid chromatography (LC) tandem mass spectrometry (MS) and inductively coupled plasma mass spectrometry (ICP-MS) were employed to target 94 organic and 55 inorganic analytes, including food and environmental contaminants (e.g., PFAS, mycotoxins, phytoestrogens, and heavy metals) as well as hormones, trace elements, metalloids and mineral elements. In a proof-of-principle study, the workflow was applied to human placental tissue and matched umbilical cord blood plasma samples from twelve individuals. In total, the workflow enables quantitative assessment of 66 to 71 targeted organic analytes, of which 24 to 35 were detected in the cord blood, cord plasma, or placental tissue samples studied. Moreover, it allowed for the quantification of 14 to 20 inorganic analytes, with another 16 to 29 analytes below the limit of detection in the biological samples. Moreover, non-targeted analysis (NTA) using high resolution MS further expanded the analyte coverage of the workflow. This first-of-its-kind approach enables (semi-)quantitative analysis of trace levels of a broad range of chemical exposures from a single sample aliquot, which is particularly advantageous when sample availability is limited.