Humans are exposed to many chemicals through various routes such as ingestion, dermal absorption, and inhalation. While many of these chemicals are known and have little-to-no risk, many more have yet to be identified which poses a continuing public health challenge. High-resolution mass spectrometry (HRMS) is the standard analytical tool for characterizing environmental contaminants, but is often employed as part of laborious and time-consuming workflows. Non-targeted analysis (NTA) methods, using HRMS, now offer higher-throughput means to simultaneously identify large numbers of unknown chemicals within a sample. To highlight the power of NTA approaches, standardized reference material house dust (SRM 2585) and human serum (SRM 1957) were evaluated using liquid chromatography electrospray ionization quadrupole time-of-flight MS. The US EPA’s Distributed Structure-Searchable Toxicity (DSSTox) database was used for chemical identification and prioritization. For initial formula assignment, MS spectra from SRM extracts were screened against ~150k unique MS-ready chemical formulae from DSSTox, with matches based on monoisotopic mass and isotope distribution. Predicted formulae were then batch-searched against DSSTox chemicals using the online US EPA CompTox Chemistry Dashboard. This search procedure yielded lists of known chemicals associated with each formula, as well as exposure and bioactivity data associated with each chemical, which were used to prioritize candidate chemicals for follow-up MS/MS analyses. Spectra from MS/MS experiments were compared against vendor-specific libraries and public databases, and used to create lists of probable chemicals in the SRMs. Results from analyses of reference standards and structure-similarity searches were used to provide semi-quantitative estimates for chemicals found in the SRMs. These results were ultimately compared to a certified list of chemicals in the mixture provided by the National Institute of Standards and Technology. Here, we present our combinatorial NTA workflow, the advantages and limitations of the methods, and semi-quantitative results for chemicals identified in reference samples.

Standardizing a standard? Identification and comparison of chemicals in standard reference materials using non-targeted analysis of organic molecules by high-resolution mass spectrometry

254th National Meeting (2017)

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