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A novel quantification method for sulfur-containing biomarkers of formaldehyde and acetaldehyde exposure in human urine and plasma samples

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Abstract

A novel method for the quantification of the sulfur-containing metabolites of formaldehyde (thiazolidine carboxylic acid (TCA) and thiazolidine carbonyl glycine (TCG)) and acetaldehyde (methyl thiazolidine carboxylic acid (MTCA) and methyl thiazolidine carbonyl glycine (MTCG)) was developed and validated for human urine and plasma samples. Targeting the sulfur-containing metabolites of formaldehyde and acetaldehyde in contrast to the commonly used biomarkers formate and acetate overcomes the high intra- and inter-individual variance. Due to their involvement in various endogenous processes, formate and acetate lack the required specificity for assessing the exposure to formaldehyde and acetaldehyde, respectively. Validation was successfully performed according to FDA’s Guideline for Bioanalytical Method Validation (2018), showing excellent performance with regard to accuracy, precision, and limits of quantification (LLOQ). TCA, TCG, and MTCG proved to be stable under all investigated conditions, whereas MTCA showed a depletion after 21 months. The method was applied to a set of pilot samples derived from smokers who consumed unfiltered cigarettes spiked with 13C-labeled propylene glycol and 13C-labeled glycerol. These compounds were used as potential precursors for the formation of 13C-formaldehyde and 13C-acetaldehyde during combustion. Plasma concentrations were significantly lower as compared to urine, suggesting urine as suitable matrix for a biomonitoring. A smoking-related increase of unlabeled biomarker concentrations could not be shown due to the ubiquitous distribution in the environment. While the metabolites of 13C-acetaldehyde were not detected, the described method allowed for the quantification of 13C-formaldehyde uptake from cigarette smoking by targeting the biomarkers 13C-TCA and 13C-TCG in urine.

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Abbreviations

AA:

Acetaldehyde

FA:

Formaldehyde

TCA:

Thiazolidine carboxylic acid

TCG:

Thiazolidine carbonyl glycine

MTCA:

Methyl thiazolidine carboxylic acid

MTCG:

Methyl thiazolidine carbonyl glycine

PCF:

Propyl chloroformate

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Acknowledgments

The authors would like to thank “Happy Liquid” Ltd., Munich, Germany, for providing the (unlabeled) e-liquids used in this study. Also, the authors would like to thank Sandy Miller (ALCS), Mohamadi Sakar (ALCS), and Jeffery Edmiston (ALCS) for their critical comments on the study design and for their input in preparing this manuscript.

Funding

This research was supported by Altria Client Services LLC (ALCS), 601 East Jackson Street, Richmond, VA 23219, USA.

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Authors and Affiliations

  1. ABF Analytisch-Biologisches Forschungslabor GmbH, Semmelweisstrasse 5, 82152, Planegg, Germany

    Anne Landmesser, Gerhard Scherer, Nikola Pluym & Max Scherer

  2. Chair for Analytical Chemistry, Technische Universität München, Marchioninistraße, 81377, Munich, Germany

    Anne Landmesser & Reinhard Niessner

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Correspondence to Max Scherer.

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Conflict of interest

Authors Gerhard Scherer, Max Scherer, Nikola Pluym, and Anne Landmesser work for ABF GmbH, Planegg, an independent contract research laboratory and declare no conflicts of interest regarding the publication of this paper. Reinhard Niessner, full Professor (emeritus) and Chair holder for Analytical Chemistry at the Technical University of Munich, Germany, declares no conflict of interest regarding the publication of this paper.

Human study

A clinical study was conducted at the Clinical Trial Center (CTC) North (Hamburg, Germany). Ethical approval was received according to the Helsinki declaration by the Ethical Commission of the Medical Chamber of Hamburg (Germany).

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Landmesser, A., Scherer, G., Pluym, N. et al. A novel quantification method for sulfur-containing biomarkers of formaldehyde and acetaldehyde exposure in human urine and plasma samples. Anal Bioanal Chem 412, 7535–7546 (2020). https://doi.org/10.1007/s00216-020-02888-y

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