Determination of specific urinary nonylphenol metabolites by online-SPE-LC-MS/MS as novel human exposure biomarkers.

J Chromatogr B Analyt Technol Biomed Life Sci

Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, Bochum 44789, Germany. Electronic address:

Published: July 2021

AI Article Synopsis

  • Nonylphenol (NP) is an endocrine disruptor commonly found in the environment and used in making certain detergents and chemicals, but human data on its metabolites are limited.
  • A new analytical method has been developed to accurately measure OH-NP and oxo-NP, oxidized forms of NP, in human urine, using advanced chromatography and mass spectrometry techniques.
  • Despite regulations in the EU, both metabolites were detected in a significant percentage of urine samples from the German population, indicating their potential as biomarkers for monitoring NP exposure in future studies.

Article Abstract

Nonylphenol (NP) is an endocrine disrupting and ecotoxic substance that has been detected in a variety of environmental matrices. It is utilized for the production of non-ionic nonylphenol ethoxylate (NPEO) detergents and other high production volume chemicals. Human biomonitoring data are scarce and mostly limited to the non-oxidized NP, which is ubiquitous in the (laboratory) environment and susceptible to external contamination. Here, we describe a sensitive, precise, accurate and rugged analytical method for the determination of OH-NP and oxo-NP, two potential alkyl-chain-oxidized metabolites of NP in human urine. We used single isomer standards, obtained by custom synthesis, for the quantification of the sum of the respective isomers. After enzymatic hydrolysis of potential urinary phase II conjugates, urine samples were analyzed by online turbulent flow chromatography for analyte enrichment and matrix depletion coupled to reversed phase liquid chromatography with negative electrospray-ionization triple quadrupole tandem mass spectrometry detection (online-SPE-LC-MS/MS). Quantification was performed by stable isotope dilution analysis. Limits of quantification in urinary matrix were 0.5 µg/L for OH-NP and 0.25 µg/L for oxo-NP. Mean relative recoveries were 101-105% (OH-NP) and 112-117% (oxo-NP) and the method imprecision (CV) in matrix was below 5%. In spite of extensive use restrictions in the EU since 2003, we could quantify OH-NP and oxo-NP in 94% and 47% of spot urine samples from the general German population (n = 32) collected in 2014. Thus, both metabolites seem suitable as sensitive and specific urinary biomarkers of NP exposure for future human biomonitoring population studies. Currently this method is used to quantitatively investigate human NP metabolism and to derive urinary metabolite excretion fractions that can be used to calculate external doses based on urinary biomarker concentrations.

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http://dx.doi.org/10.1016/j.jchromb.2021.122794DOI Listing

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