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Licensed Unlicensed Requires Authentication Published by De Gruyter January 21, 2022

Pre-analytical considerations for the analysis of uracil and 5,6-dihydrouracil in heparin plasma

Sara Capiau, Anniek Van Landschoot, Tim Reyns and Hedwig Stepman

Corresponding author: Hedwig Stepman, Department of Laboratory Medicine, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium, Phone: +32 9 332 66 47, E-mail:


The authors wish to acknowledge the laboratory technicians of Ghent University Hospital for their technical assistance in obtaining these data.

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The local Institutional Review Board approved sample collection.


1. Casneuf, V, Borbath, I, Van den Eynde, M, Verheezen, Y, Demey, W, Verstraete, AG, et al.. Joint Belgian recommendation on screening for DPD-deficiency in patients treated with 5-FU, capecitabine (and tegafur). Acta Clin Belg 2021. [Epub ahead of print].Search in Google Scholar

2. INCa and HAS. Recherche de déficit en dihydropyrimidine déshydrogenase en vue de prévenir certaines toxicités sévères survenant sous traitement comportant des fluoropyrimidines (5-fluorouracile), Recommandations et référentiels. France: INCa, HAS; décembre 2018.Search in Google Scholar

3. Meulendijks, D, Henricks, LM, Jacobs, BAW, Aliev, A, Deenen, MJ, de Vries, N, et al.. Pretreatment serum uracil concentration as a predictor of severe and fatal fluoropyrimidine-associated toxicity. Br J Cancer 2017;116:1415–24. in Google Scholar

4. Sistonen, J, Büchel, B, Froehlich, TK, Kummer, D, Fontana, S, Joerger, M, et al.. Predicting 5-fluorouracil toxicity: DPD genotype and 5,6-dihydrouracil:uracil ratio. Pharmacogenomics 2014;15:1653–66. in Google Scholar

5. Jiang, H, Lu, J, Ji, J. Circadian rhythm of dihydrouracil/uracil ratios in biological fluids: a potential biomarker for dihydropyrimidine dehydrogenase levels. Br J Pharmacol 2004;141:616–23. in Google Scholar

6. Henricks, LM, Jacobs, BAW, Meulendijks, D, Pluim, D, van den Broek, D, de Vries, N, et al.. Food-effect study on uracil and dihydrouracil plasma levels as marker for dihydropyrimidine dehydrogenase activity in human volunteers. Br J Clin Pharmacol 2018;84:2761–9. in Google Scholar

7. Jacobs, BA, Deenen, MJ, Pluim, D, van Hasselt, JG, Krähenbühl, MD, van Geel, RM, et al.. Pronounced between-subject and circadian variability in thymidylate synthase and dihydropyrimidine dehydrogenase enzyme activity in human volunteers. Br J Clin Pharmacol 2016;82:706–16. in Google Scholar

8. Jacobs, BA, Rosing, H, De Vries, N, Meulendijks, D, Henricks, LM, Schellens, JH, et al.. Development and validation of a rapid and sensitive UPLC-MS/MS method for determination of uracil and dihydrouracil in human plasma. J Pharm Biomed Anal 2016;126:75–82. in Google Scholar

9. Coudoré, F, Roche, D, Lefeuvre, S, Faussot, D, Billaud, EM, Loriot, M-A, et al.. Validation of an ultra-high performance liquid chromatography tandem mass spectrometric method for quantifying uracil and 5,6-dihydrouracil in human plasma. Chromatogr Sci 2012;50:877–84. in Google Scholar

10. CLSI. Defining, establishing, and verifying reference intervals in the clinical laboratory; Approved Guideline – Third Edition. CLSI EPC28-A3c. Wayne, PA: Clinical and Laboratory Standards Institute; 2010.Search in Google Scholar

11. Sandberg, S, Fraser, CG, Horvath, AR, Jansen, R, Jones, G, Oosterhuis, W, et al.. Defining analytical performance specifications: Consensus Statement from the 1st Strategic Conference of the European Federation of Clinical Chemistry and Laboratory Medicine. Clin Chem Lab Med 2015;53:833. in Google Scholar

12. Thomas, F, Maillard, M, Launay, M, Tron, C, Etienne-Grimaldi, M-C, Gautier-Veyret, E, et al.. Artificial increase of uracilemia during fluoropyrimidine treatment can lead to DPD deficiency misinterpretation. Ann Oncol 2021;32:810–1. in Google Scholar

Received: 2021-08-17
Accepted: 2022-01-10
Published Online: 2022-01-21
Published in Print: 2022-04-26

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