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Validated single urinary assay designed for exposomic multi-class biomarkers of common environmental exposures

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Abstract

Epidemiological studies often call for analytical methods that use a small biospecimen volume to quantify trace level exposures to environmental chemical mixtures. Currently, as many as 150 polar metabolites of environmental chemicals have been found in urine. Therefore, we developed a multi-class method for quantitation of biomarkers in urine. A single sample preparation followed by three LC injections was optimized in a proof-of-approach for a multi-class method. The assay was validated to quantify 50 biomarkers of exposure in urine, belonging to 7 chemical classes and 16 sub-classes. The classes represent metabolites of 12 personal care and consumer product chemicals (PCPs), 5 polycyclic aromatic hydrocarbons (PAHs), 5 organophosphate flame retardants (OPFRs), 18 pesticides, 5 volatile organic compounds (VOCs), 4 tobacco alkaloids, and 1 drug of abuse. Human urine (0.2 mL) was spiked with isotope-labeled internal standards, enzymatically deconjugated, extracted by solid-phase extraction, and analyzed using high-performance liquid chromatography-tandem mass spectrometry. The methanol eluate from the cleanup was split in half and the first half analyzed for PCPs, PAH, and OPFR on a Betasil C18 column; and pesticides and VOC on a Hypersil Gold AQ column. The second half was analyzed for tobacco smoke metabolites and a drug of abuse on a Synergi Polar RP column. Limits of detection ranged from 0.01 to 1.0 ng/mL of urine, with the majority ≤0.5 ng/mL (42/50). Analytical precision, estimated as relative standard deviation of intra- and inter-batch uncertainty, variabilities, was <20%. Extraction recoveries ranged from 83 to 109%. Results from the optimized multi-class method were qualified in formal international proficiency testing programs. Further method customization options were explored and method expansion was demonstrated by inclusion of up to 101 analytes of endo- and exogenous chemicals. This exposome-scale assay is being used for population studies with savings of assay costs and biospecimens, providing both quantitative results and the discovery of unexpected exposures.

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Acknowledgements

We gratefully acknowledge Dr. Dana B. Barr (Professor, Rollins School of Public Health, Emory University, Atlanta, GA, USA) for consultation for the umbelliferone validation steps and for DAPs analysis.

Funding

The Mount Sinai CHEAR/HHEAR laboratory hub acknowledges funding for this study from NIH/NIEHS: U2C ES026561 and P30 ES023515.

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Author notes

  1. Dhavalkumar Patel

    Present address: Texas Tech University Health Sciences Center, Amarillo, TX, USA

Authors and Affiliations

  1. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Ravikumar Jagani, Divya Pulivarthi, Dhavalkumar Patel, Rosalind J. Wright, Robert O. Wright, Manish Arora, Mary S. Wolff & Syam S. Andra

  2. Institute for Exposomic Research, Senator Frank R. Lautenberg Environmental Health Sciences Laboratory, Icahn School of Medicine at Mount Sinai, Atran Lab, Floor 3, Room 002, 1428 Madison Avenue, New York, NY, 10029, USA

    Ravikumar Jagani, Divya Pulivarthi, Rosalind J. Wright, Robert O. Wright, Manish Arora, Mary S. Wolff & Syam S. Andra

  3. Kravis Children’s Hospital, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Rosalind J. Wright

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  1. Ravikumar Jagani
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Correspondence to Syam S. Andra.

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Jagani, R., Pulivarthi, D., Patel, D. et al. Validated single urinary assay designed for exposomic multi-class biomarkers of common environmental exposures. Anal Bioanal Chem 414, 5943–5966 (2022). https://doi.org/10.1007/s00216-022-04159-4

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