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Chemical exposure
Electrophilic compounds as such or formed as metabolites are intrinsically reactive and can pose health risks through their interactions with biomacromolecules in vivo. These compounds are commonly found in everyday environments, including food, air pollution, cigarette smoke, and industrial settings such as chemical and drug manufacturing, as well as may release from materials like textiles and polystyrene.
Long-term chemical exposure, including to electrophilic compounds, has been associated with chronic health effects, making the assessment of their exposure a critical area of scientific and clinical research. Understanding and accurately measuring chemical exposure is essential for evaluating health risks, supporting preventative strategies, and advancing public health protection.
In addition to analyzing standard metabolic biomarkers in a routine biomonitoring set-up, we provide the possibility to investigate which can be the most optimal biomarker applying our state-of-the-art instrumentation, methodologies and vast experience in ADME including structural characterization of analytes in different matrices. This is particularly useful since many current biomarkers are a result of traditional approaches and/or simplicity.
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• Urinary metabolites analysis
Urinary biomarkers for assessing chemical exposure and metabolism
Urinary metabolite analysis is a widely used approach in biomonitoring to assess human exposure to chemicals. Instead of measuring the parent compound directly (which may be short-lived in the body), one can quantify specific metabolites excreted in urine. This method is non-invasive, sensitive, and suitable for getting a snapshot of the exposure and in some cases useful for large population studies.
This approach is particularly applicable for compounds like acrylamide, which is not only reactive, but also rapidly metabolized and therefore direct measurement is not an optimal approach. Acrylamide is formed during high-temperature cooking of carbohydrate-rich foods and is also encountered in certain occupational settings. Once absorbed, it undergoes biotransformation through conjugation with glutathione or oxidation to glycidamide, a more reactive and potentially genotoxic metabolite. These metabolic pathways give rise to specific urinary biomarkers that can be quantified to estimate internal exposure.
In addition to urinary biomarkers, stable metabolites or conjugates formed from electrophilic compounds can also be measured in plasma and serum, providing complementary information on internal exposure.
Our service
- We provide expert characterization and quantification of metabolic biomarkers in clinical samples, including urine as well as plasma and serum
- Advanced LC-HRMS–based analysis for high sensitivity and accuracy
- Comprehensive exposure profiling in biological samples
- High-throughput workflows enabling efficient analysis of large sample sets
- For blood samples, we recommend protein adduct analysis, a robust and well-established approach that offers several distinct advantages, including improved exposure integration over time and enhanced analytical reliability. Read more about the benefits of hemoglobin adduct analysis below.
• Hemoglobin adduct analysis
Determination of chemical exposure as a basis for human biomonitoring and risk assessment – focus on alkylating compounds
Assessing exposure to electrophilic compounds and metabolites is challenging due to their inherent reactivity. However, structural modifications on blood proteins and nucleic acids, forming adducts, can serve as valuable biomarkers of exposure to both exogenous and endogenous electrophiles. Hemoglobin adducts, in particular, enable evaluation of exposure to specific alkylating agents in epidemiological studies and in estimating occupational exposure, as well as in tracing reactive drug metabolites. We have applied this approach to hemoglobin adducts of low molecular weight alkylating compounds, including acrylamide and its metabolite glycidamide [1], as well as ethylene oxide, acrylonitrile and glycidol.
Our service
- We employ high-resolution mass spectrometry (HRMS)-based methods to analyze adducts to hemoglobin. This includes applying the FIRE method [2,3], which is a development of the modified Edman degradation – the adduct is derivatized and released with the N-terminal valine tag. The corresponding analyte specific to the electrophile is enriched by SPE and quantified by LC-HRMS. HRMS data combined with expert knowledge is used for profiling and characterization of the adducts.
- Depending on the research question, analyses can be conducted across various species and sample types, such as whole blood or dried blood spots.
[1] Quantitative analysis of exposure to electrophiles using blood samples: Method evaluation using acrylamide and glycidamide as model compound. Toxicol Lett. Vol 411, 2025.
[2] A new modified Edman procedure for analysis of N-terminal valine adducts in hemoglobin by LC-MS/MS. J Chromatogr B. Vol 878, 2010.
[3] Estimation of intake and quantification of hemoglobin adducts of acrylamide in adolescents in Sweden. Front Nutr. Vol 11, 2024.
