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A “dilute-and-shoot” column-switching UHPLC–MS/MS procedure for the rapid determination of branched nonylphenol in human urine: method optimisation and some fundamental aspects of nonylphenol analysis

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Abstract

Technical grade branched nonylphenol (NP) was determined in human urine by online solid phase extraction–ultra high-performance liquid chromatography–tandem mass spectrometry (SPE–UHPLC–MS/MS). Prior to analysis, urine specimens were simply diluted and enzymatically deconjugated. The run time of the chromatography, including SPE and re-equilibration, was 9 min per injection. The enzymatic cleavage of NP conjugates was optimised with incurred sample material from a human metabolism study: the highest recoveries were obtained with β-glucuronidase from E. coli K 12 in 0.1 M ammonium acetate at pH 6.5, within a minimal hydrolysis time of 30 to 60 min. Using sodium acetate instead of ammonium acetate led to systematically decreased recovery rates. The analytical method was validated regarding its precision (coefficients of variation: 2.9–7.4%), accuracy (relative recovery rates: 93–105%), robustness (relative recovery rates in individual urine matrices: 92–117%), selectivity, and limit of quantification (1.0 μg L−1). Fundamental aspects in the analysis of technical product mixtures such as NP, comprising various isomers and homologues, were considered. Validation results, an exposure scenario and the application of the procedure to real samples, show that it enables a rugged monitoring of NP exposures above, at, and significantly below health-based guidance values, corresponding to daily NP intakes in the low μg kg−1 d−1 range. On the other hand, background levels in non-specifically exposed populations cannot be detected with this method. Hence, while alternative approaches should be pursued for NP analysis at environmental trace level, the speed and simplicity of our method are ideal for high-throughput human biomonitoring in occupational medicine.

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Notes

  1. “Quaternary” in this paper means that the α-C is bonded to four other carbon atoms: one carbon atom in the aromatic ring plus three alkyl carbons (HO-Ph-CR1R2R3). Accordingly, a “tertiary” α-C would be bonded to the ring, to two alkyl carbons and to one hydrogen atom (HO-Ph-CHR1R2); a “secondary” α-C to the ring, to one alkyl carbon and to two hydrogens (HO-Ph-CH2R1). In some other publications, e.g. [3, 32], the nomenclature is handled differently, from the point of view of the branched nonyl moiety: “tertiary” would designate structures of the HO-Ph-CR1R2R3 type etc.

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Acknowledgements

We thank Sandra Röhrig (Currenta) for measuring the creatinine contents of urine samples. Special thanks go to Holger M. Koch, Benedikt Ringbeck, Thomas Brüning and Frederik Lessmann (IPA – Institute for Prevention and Occupational Medicine, Bochum) for performing the human metabolism study as well as to the anonymous donors of urine samples. Severin Müller and Hans Certa (SI Group) are acknowledged for kindly supplying the branched NP reference material. Vladimir N. Belov (Max Planck Institute for Biophysical Chemistry, Göttingen) synthesised and generously provided technical grade NP-13C6 as a reference material.

Funding

The development of the analytical method and its application in investigating human metabolism and population samples are part of a large-scale project on the advancement of human biomonitoring in Germany. This project is a cooperation agreed in 2010 between the Federal Ministry for the Environment, Nature Conservation, and Nuclear Safety (BMU) and the Verband der chemischen Industrie e.V. (German Chemical Industry Association – VCI) and is managed by the German Environment Agency (UBA). Experts from governmental scientific authorities, industry and science accompany the project in substance selection and method development. The present study was financed by the Chemie Wirtschaftsförderungs-GmbH, Mainzer Landstraße 55, 60329 Frankfurt (Germany).

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Author notes

  1. Wolfgang Gries

    Present address: Currenta GmbH & Co. OHG, Environmental Analytics, Chempark Gebäude R 800, 47829, Krefeld-Uerdingen, Germany

  2. Christoph Schmidtkunz and Wolfgang Gries contributed equally.

Authors and Affiliations

  1. Currenta GmbH & Co. OHG, Institute of Biomonitoring, Chempark Gebäude Q 18, 51368, Leverkusen, Germany

    Christoph Schmidtkunz, Wolfgang Gries, Katja Küpper & Gabriele Leng

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Contributions

Christoph Schmidtkunz: Writing, original draft; conceptualisation (exposure modelling); formal analysis; visualisation. Wolfgang Gries: Conceptualisation (laboratory studies); formal analysis; validation; writing, review and editing; project administration; funding acquisition. Katja Küpper: Methodology, validation, investigation. Gabriele Leng: Writing, review and editing; supervision; funding acquisition.

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Correspondence to Christoph Schmidtkunz.

Ethics declarations

Ethics approval and source of biological material

The oral dose study [26] in which human urine samples were obtained for the purpose of metabolism investigation and method development complied with the Code of Ethics of the World Medical Association (1964 Declaration of Helsinki, including its later amendments). It had been reviewed by the Ethics Commission of the Medical Faculty of the Ruhr-Universität Bochum under the reg. no. 15–5433. Written informed consent was provided by each participant of the study, after receiving the study design in written form [26].

Forty spot urine samples from persons without occupational exposure to NP were sourced in the occupational biomonitoring programmes of our company. The participants in these programmes are comprehensively informed by occupational physicians of the Department of Health Protection about the biomonitoring examinations at the Institute of Biomonitoring. Participation is strictly voluntary for each worker and requires his or her informed consent.

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Schmidtkunz, C., Gries, W., Küpper, K. et al. A “dilute-and-shoot” column-switching UHPLC–MS/MS procedure for the rapid determination of branched nonylphenol in human urine: method optimisation and some fundamental aspects of nonylphenol analysis. Anal Bioanal Chem 415, 975–989 (2023). https://doi.org/10.1007/s00216-022-04495-5

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