SAFE USE OF FLUOROPYRIMIDINES IN ONCOLOGY: DEVELOPMENT OF A METHOD FOR THE DETERMINATION OF PLASMA URACIL AND DIHYDROURACIL LEVELS BY UHPLC-MS-MS AND SCREENING FOR DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY

Authors

  • Farida Bouchenak Toxicology Laboratory, Central Army Hospital Dr. Mohamed Seghir Nekkache, Algeria
  • Nardjess Rim Laoufi Toxicology Laboratory, Central Army Hospital Dr. Mohamed Seghir Nekkache, Algeria
  • Khaled Sobhi Toxicology Laboratory, Central Army Hospital Dr. Mohamed Seghir Nekkache, Algeria
  • Djamal Sadouki Toxicology Laboratory, Central Army Hospital Dr. Mohamed Seghir Nekkache, Algeria
  • Mohammed Hazi Medical Oncology. Central Army Hospital Dr. Mohamed Seghir Nekkache, Algeria
  • Samir Adjmi Medical Oncology. Central Army Hospital Dr. Mohamed Seghir Nekkache, Algeria
  • Kamel Mansouri Pharmacology Laboratory. Faculty of Pharmacy. University of Algiers I
  • Kamel Bouzid Medical Oncology. Centre Pierre Marie Curie (CPMC), Algeria

DOI:

https://doi.org/10.4314/jfas.1320

Keywords:

Uracil, Screening, ; DPD Deficiency., Fluoropyrimidines

Abstract

5-Fluorouracil (5-FU) is a widely used drug in oncology. It can cause toxicity, especially in the case of Dihydropyrimidine Dehydrogenase (DPD) deficiency. An enzyme responsible for the inactivation of more than 80% of the 5-FU dose and for the transformation of uracil (U) into dihydrouracile (UH2). A sensitive method is needed to screen for DPD deficiency by determination of U level, as recommended by the European Medicine Agency (EMA). Separation was performed by an UHPLC on a C18 column and a tandem mass spectrometer performed the detection of U and UH2. The method’s performance was validated according to ICH M10 recommendations. The validated method was used to screen for DPD deficiency in fifty-seven hospitalized patients. None of the patients showed DPD deficiency based on the U-rate instead of the metabolic ratio UH2/U (7.08%) which might be a more sensitive tool for this screening.

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References

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Published

2023-04-02

How to Cite

BOUCHENAK, F.; LAOUFI, N. R.; SOBHI, K.; SADOUKI, D.; HAZI, M.; ADJMI, S.; MANSOURI, K.; BOUZID, K. SAFE USE OF FLUOROPYRIMIDINES IN ONCOLOGY: DEVELOPMENT OF A METHOD FOR THE DETERMINATION OF PLASMA URACIL AND DIHYDROURACIL LEVELS BY UHPLC-MS-MS AND SCREENING FOR DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY . Journal of Fundamental and Applied Sciences, [S. l.], v. 15, n. 2, p. 160–175, 2023. DOI: 10.4314/jfas.1320. Disponível em: https://jfas.info/index.php/JFAS/article/view/1320. Acesso em: 21 jun. 2024.

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