Quantitative impact of pre‐analytical process on plasma uracil when testing for dihydropyrimidine dehydrogenase deficiency

Determining dihydropyrimidine dehydrogenase (DPD) activity by measuring patient's uracil (U) plasma concentration is mandatory before fluoropyrimidine (FP) administration in France. In this study, we aimed to refine the pre‐analytical recommendations for determining U and dihydrouracil (UH2) concentrations, as they are essential in reliable DPD‐deficiency testing.

[1]  J. Phelip,et al.  Clinical considerations for DPD deficiency testing in advanced cancer patients: tumor lysis syndrome should be considered as a major interference. , 2022, Annals of oncology : official journal of the European Society for Medical Oncology.

[2]  A. V. van Kuilenburg,et al.  Dihydropyrimidine Dehydrogenase Phenotyping Using Pretreatment Uracil: A Note of Caution Based on a Large Prospective Clinical Study , 2022, Clinical pharmacology and therapeutics.

[3]  H. Stepman,et al.  Pre-analytical considerations for the analysis of uracil and 5,6-dihydrouracil in heparin plasma , 2022, Clinical chemistry and laboratory medicine.

[4]  M. Loriot,et al.  Pretherapeutic screening for Dihydropyrimidine deshydrogenase deficiency in measuring uracilemia in dialysis patients leads to a high rate of falsely positive results , 2021, Cancer Chemotherapy and Pharmacology.

[5]  J. Guitton,et al.  Issues and limitations of available biomarkers for fluoropyrimidine-based chemotherapy toxicity, a narrative review of the literature , 2021, ESMO open.

[6]  Jacob E. Wulff,et al.  Global biochemical analysis of plasma, serum and whole blood collected using various anticoagulant additives , 2021, PloS one.

[7]  V. Haufroid,et al.  Artificial increase of uracilemia during fluoropyrimidine treatment can lead to DPD deficiency misinterpretation. , 2021, Annals of oncology : official journal of the European Society for Medical Oncology.

[8]  M. Loriot,et al.  A comprehensive population-based study comparing the phenotype and genotype in a pretherapeutic screen of dihydropyrimidine dehydrogenase deficiency , 2020, British Journal of Cancer.

[9]  P. Marquet,et al.  Phenotyping of uracil and 5-fluorouracil metabolism using LC-MS/MS for prevention of toxicity and dose adjustment of fluoropyrimidines. , 2020, Therapeutic drug monitoring.

[10]  C. Solas,et al.  A Simple and Rapid UPLC‐UV Method for Detecting DPD Deficiency in Patients With Cancer , 2020, Clinical and translational science.

[11]  G. Defossez,et al.  Toxicities associated with chemotherapy regimens containing a fluoropyrimidine: A real-life evaluation in France. , 2019, European journal of cancer.

[12]  M. Loriot,et al.  [Dihydropyrimidine dehydrogenase deficiency screening for management of patients receiving a fluoropyrimidine: Results of two national practice surveys addressed to clinicians and biologists]. , 2019, Bulletin du cancer.

[13]  J. Schellens,et al.  Food‐effect study on uracil and dihydrouracil plasma levels as marker for dihydropyrimidine dehydrogenase activity in human volunteers , 2018, British journal of clinical pharmacology.

[14]  J. Schellens,et al.  The impact of liver resection on the dihydrouracil:uracil plasma ratio in patients with colorectal liver metastases , 2018, European Journal of Clinical Pharmacology.

[15]  C. Florkowski,et al.  evelopment , validation and application of a novel liquid hromatography tandem mass spectrometry assay measuring uracil , , 6-dihydrouracil , 5-fluorouracil , 5 , 6-dihydro-5-fluorouracil ,-fluoro-- ureidopropionic acid and-fluoro-- alanine in human lasma , 2017 .

[16]  J. Schellens,et al.  Pretreatment serum uracil concentration as a predictor of severe and fatal fluoropyrimidine-associated toxicity , 2017, British Journal of Cancer.

[17]  J. Schellens,et al.  Pronounced between-subject and circadian variability in thymidylate synthase and dihydropyrimidine dehydrogenase enzyme activity in human volunteers. , 2016, British journal of clinical pharmacology.

[18]  J. Schellens,et al.  Development and validation of a rapid and sensitive UPLC-MS/MS method for determination of uracil and dihydrouracil in human plasma. , 2016, Journal of pharmaceutical and biomedical analysis.

[19]  J. Sanderson,et al.  Clinical relevance of DPYD variants c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity: a systematic review and meta-analysis of individual patient data. , 2015, The Lancet. Oncology.

[20]  G. Schwartsmann,et al.  Improved determination of uracil and dihydrouracil in plasma after a loading oral dose of uracil using high-performance liquid chromatography with photodiode array detection and porous graphitic carbon stationary phase. , 2015, Clinical biochemistry.

[21]  J. Schellens,et al.  Translating DPYD genotype into DPD phenotype: using the DPYD gene activity score. , 2015, Pharmacogenomics.

[22]  A. V. van Kuilenburg,et al.  Predicting 5-fluorouracil toxicity: DPD genotype and 5,6-dihydrouracil:uracil ratio. , 2014, Pharmacogenomics.

[23]  U. Amstutz,et al.  LC-MS/MS method for simultaneous analysis of uracil, 5,6-dihydrouracil, 5-fluorouracil and 5-fluoro-5,6-dihydrouracil in human plasma for therapeutic drug monitoring and toxicity prediction in cancer patients. , 2013, Biomedical chromatography : BMC.

[24]  M. Loriot,et al.  Validation of an ultra-high performance liquid chromatography tandem mass spectrometric method for quantifying uracil and 5,6-dihydrouracil in human plasma. , 2012, Journal of chromatographic science.

[25]  G. A. Pianetti,et al.  A Rapid HPLC-ESI-MS/MS Method for Determination of Dihydrouracil/Uracil Ratio in Plasma: Evaluation of Toxicity to 5-Flurouracil in Patients With Gastrointestinal Cancer , 2012, Therapeutic drug monitoring.

[26]  Fabio Garofolo,et al.  Impact of plasma and whole-blood anticoagulant counter ion choice on drug stability and matrix effects during bioanalysis. , 2009, Bioanalysis.

[27]  M. Egorin,et al.  Quantitation of 5-fluorouracil (5-FU) in human plasma by liquid chromatography/electrospray ionization tandem mass spectrometry. , 2008, Rapid communications in mass spectrometry : RCM.

[28]  E. Gamelin,et al.  5-Fluorouracil-related severe toxicity: a comparison of different methods for the pretherapeutic detection of dihydropyrimidine dehydrogenase deficiency. , 2007, Cancer letters.

[29]  R. Diasio,et al.  Increased Prevalence of Dihydropyrimidine Dehydrogenase Deficiency in African-Americans Compared with Caucasians , 2006, Clinical Cancer Research.

[30]  E. Gamelin,et al.  An accurate dihydrouracil/uracil determination using improved high performance liquid chromatography method for preventing fluoropyrimidines-related toxicity in clinical practice. , 2005, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[31]  Hao Jiang,et al.  Circadian rhythm of dihydrouracil/uracil ratios in biological fluids: a potential biomarker for dihydropyrimidine dehydrogenase levels , 2004, British journal of pharmacology.

[32]  A. V. van Kuilenburg.  Dihydropyrimidine dehydrogenase and the efficacy and toxicity of 5-fluorouracil. , 2004, European journal of cancer.

[33]  J. Leffert,et al.  Homeostatic control of uridine and the role of uridine phosphorylase: a biological and clinical update. , 2002, Biochimica et biophysica acta.

[34]  O. Dassonville,et al.  [Population study of dihydropyrimidine dehydrogenase in cancer patients]. , 1994, Bulletin du cancer.