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

Auteurs

Maggy Lépine, IRSSTFollow
Lekha Sleno, UQAMFollow
Jacques Lesage, Université du Québec à MontréalFollow
Sébastien Gagné, IRSSTFollow

Type de document

Études primaires

Année de publication

2020

Langue

Anglais

Titre de la revue

Analytical and Bioanalytical Chemistry

Première page

753

Dernière page

762

Résumé

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.

Mots-clés

Isocyanates, Évaluation de l'exposition, Exposure evaluation, Dosage dans l'urine, Determination in urine, Échantillonnage et analyse, Sampling and analysis

Numéro de projet IRSST

n/a

Citation recommandée

Lépine, M., Sleno, L., Lesage, J. et Gagné, S. (2020). A validated UPLC-MS/MS method for the determination of aliphatic and aromatic isocyanate exposure in human urine. Analytical and Bioanalytical Chemistry, 412(3), 753-762. https://doi.org/10.1007/s00216-019-02295-y