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Expanded coverage of non-targeted LC-HRMS using atmospheric pressure chemical ionization: a case study with ENTACT mixtures

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Abstract

Non-targeted analysis (NTA) is a rapidly evolving analytical technique with numerous opportunities to improve and expand instrumental and data analysis methods. In this work, NTA was performed on eight synthetic mixtures containing 1264 unique chemical substances from the U.S. Environmental Protection Agency’s Non-Targeted Analysis Collaborative Trial (ENTACT). These mixtures were analyzed by atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI) using both positive and negative polarities for a total of four modes. Out of the 1264 ENTACT chemical substances, 1116 were detected in at least one ionization mode, 185 chemicals were detected using all four ionization modes, whereas 148 were not detected. Forty-four chemicals were detected only by APCI, and 181 were detected only by ESI. Molecular descriptors and physicochemical properties were used to assess which ionization type was preferred for a given compound. One ToxPrint substructure (naphthalene group) was found to be enriched in compounds only detected using APCI, and eight ToxPrints (e.g., several alcohol moieties) were enriched in compounds only detected using ESI. Examination of physicochemical parameters for ENTACT chemicals suggests that those with higher aqueous solubility preferentially ionized by ESI−. While ESI typically detects a larger number of compounds, APCI offers chromatograms with less background, fewer co-elutions, and additional chemical space coverage, suggesting both should be considered for broader coverage in future NTA research.

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Data availability

The datasets generated during and/or analyzed during the current study are available in the EPA’s ScienceHub and/or the accompanying supporting information.

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Acknowledgments

The authors would like to acknowledge support from the Oak Ridge Institute for Science and Education and Luxembourg National Research Fund for project A18/BM/12341006. Special thanks to Chris Grulke and Antony Williams for their support with ENTACT and related data, Daniel Todd for assistance with the LC/MS analysis, and James McCord for scientific discussions.

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Authors and Affiliations

  1. Oak Ridge Institute for Science and Education Fellow, United States Environmental Protection Agency, Office of Research & Development, National Exposure Research Laboratory, Research Triangle Park, NC, 27711, USA

    Randolph R. Singh & Alex Chao

  2. Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6, avenue du Swing, 4367, Belvaux, Luxembourg

    Randolph R. Singh & Emma L. Schymanski

  3. U.S. Environmental Protection Agency, Office of Research & Development, National Exposure Research Laboratory, 109 TW Alexander Dr., Research Triangle Park, NC, 27711, USA

    Katherine A. Phillips, Jon R. Sobus & Elin M. Ulrich

  4. Department of Biological Sciences, North Carolina State University, Raleigh, NC, 27695, USA

    Xin Rui Xia & Damian Shea

  5. Statera Environmental Inc., 5116 Olde South Road, Raleigh, NC, 27606, USA

    Xin Rui Xia & Damian Shea

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  1. Randolph R. Singh
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Correspondence to Elin M. Ulrich.

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The views expressed in this article are those of the authors and do not necessarily represent the views or policies of the U.S. Environmental Protection Agency.

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Published in the topical collection Persistent and Mobile Organic Compounds – An Environmental Challenge with guest editors Torsten C. Schmidt, Thomas P. Knepper, and Thorsten Reemtsma.

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Singh, R.R., Chao, A., Phillips, K.A. et al. Expanded coverage of non-targeted LC-HRMS using atmospheric pressure chemical ionization: a case study with ENTACT mixtures. Anal Bioanal Chem 412, 4931–4939 (2020). https://doi.org/10.1007/s00216-020-02716-3

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