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Cancer Chemotherapy and Pharmacology

Erschienen in:

11.03.2023 | Original Article

Assay performance and stability of uracil and dihydrouracil in clinical practice

verfasst von: Jonathan E. Knikman, Hilde Rosing, Henk-Jan Guchelaar, Annemieke Cats, Jos H. Beijnen

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 3/2023

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Abstract

Purpose

Measurement of endogenous uracil (U) is increasingly being used as a dose-individualization method in the treatment of cancer patients with fluoropyrimidines. However, instability at room temperature (RT) and improper sample handling may cause falsely increased U levels. Therefore we aimed to study the stability of U and dihydrouracil (DHU) to ensure proper handling conditions.

Methods

Stability of U and DHU in whole blood, serum, and plasma at RT (up to 24 h) and long-term stability (≥ 7 days) at − 20 °C were studied in samples from 6 healthy individuals. U and DHU levels of patients were compared using standard serum tubes (SSTs) and rapid serum tubes (RSTs). The performance of our validated UPLC-MS/MS assay was assessed over a period of 7 months.

Results

U and DHU levels significantly increased at RT in whole blood and serum after blood sampling with increases of 12.7 and 47.6% after 2 h, respectively. A significant difference (p = 0.0036) in U and DHU levels in serum was found between SSTs and RSTs. U and DHU were stable at − 20 °C at least 2 months in serum and 3 weeks in plasma. Assay performance assessment fulfilled the acceptance criteria for system suitability, calibration standards, and quality controls.

Conclusion

A maximum of 1 h at RT between sampling and processing is recommended to ensure reliable U and DHU results. Assay performance tests showed that our UPLC-MS/MS method was robust and reliable. Additionally, we provided a guideline for proper sample handling, processing and reliable quantification of U and DHU.

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Titel: Assay performance and stability of uracil and dihydrouracil in clinical practice
verfasst von: Jonathan E. Knikman
Hilde Rosing
Henk-Jan Guchelaar
Annemieke Cats
Jos H. Beijnen
Publikationsdatum: 11.03.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 3/2023
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-023-04518-7

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Assay performance and stability of uracil and dihydrouracil in clinical practice

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