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A sensitive GC–MS/MS method for the quantification of benzo[a]pyrene tetrol in urine

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Abstract

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants formed during the incomplete combustion of organic matter such as tobacco. Among these, benzo[a]pyrene (BaP) has been classified as a known carcinogen to humans. It unfolds its effect through metabolic activation to BaP-(7R,8S)-diol-(9S,10R)-epoxide (BPDE), the ultimate carcinogen of BaP. In this article, we describe a simple and highly sensitive GC–NICI–MS/MS method for the quantification of urinary BaP-(7R,8S,9R,10S)-tetrol (( +)-BPT I-1), the hydrolysis product of BPDE. The method was validated and showed excellent results in terms of accuracy, precision, and sensitivity (lower limit of quantification (LLOQ): 50 pg/L). In urine samples derived from users of tobacco/nicotine products and non-users, only consumption of combustible cigarettes was associated with a significant increase in BPT I-1 concentrations (0.023 ± 0.016 nmol/mol creatinine, p < 0.001). Levels of users of potentially reduced-risk products as well as non-users were all below the LLOQ. In addition, the urine levels of six occupationally exposed workers were analyzed and showed the highest overall concentrations of BPT I-1 (844.2 ± 336.7 pg/L). Moreover, comparison with concentrations of 3-hydroxybenzo[a]pyrene (3-OH-BaP), the major detoxification product of BaP oxidation, revealed higher levels of 3-OH-BaP than BPT I-1 in almost all study subjects. Despite the lower levels, BPT I-1 can provide more relevant information on an individual’s cancers susceptibility since BPDE is generated by the metabolic activation of BaP. In conclusion, BPT I-1 is a suitable biomarker to distinguish not only cigarette smokers from non-smokers but also from users of potentially reduced-risk products.

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Abbreviations

AMS:

Accelerator mass spectrometry

APLI:

Atmospheric pressure laser ionization

Bap:

Benzo[a]pyrene

BPT I-1:

trans, anti-Benzo[a]pyrene tetrol

BPT I-2:

cis, anti-Benzo[a]pyrene tetrol

BPT II-1:

trans, syn-Benzo[a]pyrene tetrol

BPT II-2:

cis, syn-Benzo[a]pyrene tetrol

BPDE :

Benzo[a]pyrene-(7R,8S)-diol-(9S,10R)-epoxide

reverse-BPDE :

Benzo[a]pyrene -(9S,10R)-diol-(7R,8S)-epoxide

CV :

Coefficient of variation

CC :

Combustible cigarette

CE:

Collision energy

CYP :

Cytochrome P450

EC:

Electronic cigarette

EH :

Epoxide hydrolase

FMV:

First morning void

GC:

Gas chromatography

HTP :

Heated tobacco product

HBM :

Human biomonitoring

3-OH-BaP :

3-Hydroxybenzo[a]pyrene

IS :

Internal standard

IQR :

Interquartile range

LLOQ :

Lower limit of quantification

LOD :

Limit of detection

MS :

Mass spectrometry

NICI :

Negative ion chemical ionization

NRT :

Nicotine replacement therapy

NU :

Non-users

OT :

Oral tobacco

PAH :

Polycyclic aromatic hydrocarbon

PTV :

Programmed temperature vaporization

QC :

Quality control

MS/MS :

Tandem mass spectrometry

TMS :

Trimethylsilyl

UHPLC :

Ultra-high performance liquid chromatography

ULOQ :

Upper limit of quantification

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Acknowledgements

The authors would like to thank Alpeshkumar Kachhadia and Therese Burkhardt for their support and for contributing to helpful scientific discussions. We thank Nadine Rögner and Marta Latawiec for the measurement of 3-OH-BaP, Michael Sprenzel for measuring creatinine values, and Kira Pormann for support with the study sample analysis.

Funding

This study was funded with a grant from the Foundation for a Smoke-Free World. The Foundation for a Smoke-Free World is an independent, US nonprofit 501(c)(3) grantmaking organization with the purpose of improving global health by ending smoking in this generation. Through September 2023, the Foundation received charitable gifts from PMI Global Services Inc. (“PMI”). Independent from PMI since its founding in 2017, the Foundation operates in a manner that ensures its independence from PMI and any commercial entity. The Foundation seeks to collaborate with associations and institutions to accelerate its investments in life-saving research projects.

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Authors and Affiliations

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

    Fabian Pilz, Antonia Gärtner, Nikola Pluym, Gerhard Scherer & Max Scherer

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  1. Fabian Pilz
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  2. Antonia Gärtner
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  3. Nikola Pluym
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  4. Gerhard Scherer
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  5. Max Scherer
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Contributions

Conceptualization: F.P., N.P., G.S., and M.S. Methodology: F.P., N.P., and M.S. Formal analysis and investigation: F.P. and A.G. Validation: F.P. and A.G.; Visualization: F.P. Writing—original draft preparation: F.P. Writing—review and editing: M.S. and F.P. Funding acquisition: M.S. Supervision: M.S. and N.P. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Max Scherer.

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Ethics approval

A clinical study was conducted at the Clinical Trial Center (CTC) North (Hamburg, Germany) [39]. For all collected study samples, ethical approval was received according to the Helsinki declaration by the Ethical Commission of the Medical Chamber of Hamburg (Germany).

Conflict of interest

The authors declare no competing financial as well as nonfinancial interests. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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Pilz, F., Gärtner, A., Pluym, N. et al. A sensitive GC–MS/MS method for the quantification of benzo[a]pyrene tetrol in urine. Anal Bioanal Chem 416, 2913–2928 (2024). https://doi.org/10.1007/s00216-024-05233-9

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