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A validated UPLC-MS/MS method for the determination of aliphatic and aromatic isocyanate exposure in human urine

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Abstract

4,4′-Methylenediphenyldiisocyanate (MDI), toluenediisocyanate (2,4-TDI and 2,6-TDI), and 1,6′-hexamethylenediisocyanate (HDI) are all commonly used in the production of polyurethane-containing materials in different application areas. Workers exposed occupationally to these compounds may develop sensitization with the potential to lead to asthma. Isocyanates are metabolized in vivo by conjugation to macromolecules and/or by acetylation prior to being eliminated in urine. The hydrolysis of urine samples releases free amine compounds from these metabolites as biomarkers of exposure, specific to each parent isocyanate: 4,4′-methylenedianiline (MDA), toluenediamine (2,4-TDA and 2,6-TDA), and hexamethylenediamine (HDA). To address the need for a validated method that could be used for the simultaneous determination of biomarkers of aliphatic and aromatic isocyanates to monitor occupational exposure based on recommended thresholds, we have developed an UPLC-MS/MS method for the quantitation of MDA, TDA isomers, and HDA following acid hydrolysis, solid-phase extraction, and derivatization of urine samples. Free amine compounds were derivatized with acetic anhydride to augment chromatographic retention and signal intensity. The method was developed considering the biological guidance value (BGV) of MDA at 10 μg L−1, and biological exposure indices (BEI) of TDA isomers and HDA at 5 μg g−1 and 15 μg g−1 creatinine, respectively. Limits of detection allowed monitoring down to 6% of BGV/BEI, with precision within 8%. The accuracy and reliability of the method were assessed using inter-laboratory reference samples and deemed acceptable based on three rounds of measurements. This novel method has therefore been proven as useful for occupational safety and health assessments.

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Authors and Affiliations

  1. Chemistry Department, Université du Québec à Montréal, PO Box 8888 Downtown Station, Montreal, H3C 3P8, Canada

    Maggy Lépine, Lekha Sleno & Jacques Lesage

  2. Institut de recherche Robert-Sauvé en santé et en sécurité du travail, 505 boul. De Maisonneuve Ouest, Montréal, Québec, H3A 3C2, Canada

    Maggy Lépine & Sébastien Gagné

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  1. Maggy Lépine
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  2. Lekha Sleno
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Correspondence to Lekha Sleno or Sébastien Gagné.

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Lépine, M., Sleno, L., Lesage, J. et al. A validated UPLC-MS/MS method for the determination of aliphatic and aromatic isocyanate exposure in human urine. Anal Bioanal Chem 412, 753–762 (2020). https://doi.org/10.1007/s00216-019-02295-y

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