ArticleRapid communications in mass spectrometry : RCM2019
A simplified method for detection of N-terminal valine adducts in patients receiving treosulfan.
Article in Rapid communications in mass spectrometry : RCM, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- Sex-Specific Formation of 1,2:3,4-Diepoxybutane-Derived Hemoglobin Adducts in 1,3-Butadiene-Exposed Workers.Chemical research in toxicology · 2025Article
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- Characterization of population variability of 1,3-butadiene derived protein adducts in humans and mice.Regulatory toxicology and pharmacology : RTP · 2022Article
- Quo vadis blood protein adductomics?Archives of toxicology · 2022Review
- Lung metabolome of 1,3-butadiene exposed Collaborative Cross mice reflects metabolic phenotype of human lung cancer.Toxicology · 2021Article
- Effects ofChemical research in toxicology · 2021Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
rationaleTreosulfan is a substance that is being studied as part of the conditioning regimen given prior to allogeneic stem cell transplantation in patients with hematological malignancies. It is known to decompose into 1,2:3,4-diepoxybutane (DEB) under physiologic conditions. In this study, we investigate whether N-terminal valine adducts can be utilized to monitor differences in DEB formation of patients receiving treosulfan as part of the conditioning regimen for transplantation.
methodsBlood samples were collected from a group of 14 transplant recipients and analyzed for N,N-(2,3-dihydroxy-1,4-butadiyl)valine (pyr-Val) and 2,3,4-trihydroxybutylvaline (THB-Val) adducts as biomarkers for drug uptake and metabolism before treosulfan treatment and 6 days after treatment.
resultsA new direct injection liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated prior to clinical analysis. The assay precision was determined by 3 replicate analyses on 3 individual days using control globin spiked with known amounts of pyr-Val and THB-Val. The intra- and inter-day precision coefficients of variance (CVs) and accuracy were < 10% and 15%, respectively. In clinical specimens, the means ± SD of pyr-Val and THB-Val background were 0.29 ± 0.10 pmol/g HB and 5.17 ± 1.7 pmol/g HB, respectively.
conclusionsThese values are similar to those found previously. Treosulfan treatment leads to a significant increase in pyr-Val and THB-Val adducts in each patient (Student's t-test p <0.0001). The mean ± SD amounts of adduct formed were 245.3 ± 89.6 and 210 ± 78.5 pmol/g globin for pyr-Val and THB-Val, respectively. Importantly, these results show that this direct injection method can quantitate both background and treosulfan-induced pyr-Val and THB-Val N-terminal valine globin adducts in humans.
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