Title: A simple and rapid high-performance liquid chromatographic (HPLC) method for 5-fluorouracil (5-FU) assay in plasma and possible detection of patients with impaired dihydropyrimidine dehydrogenase (DPD) activity
Abstract: Journal of Clinical Pharmacy and TherapeuticsVolume 29, Issue 4 p. 307-315 A simple and rapid high-performance liquid chromatographic (HPLC) method for 5-fluorouracil (5-FU) assay in plasma and possible detection of patients with impaired dihydropyrimidine dehydrogenase (DPD) activity J. Ciccolini PharmD PhD, J. Ciccolini PharmD PhD Fédération et Pharmacologie Clinique et Médicale et de Pharmacocinétique, MarseilleSearch for more papers by this authorC. Mercier MD, C. Mercier MD Service d'Oncologie Médicale, La Timone University Hospital, Marseille, FranceSearch for more papers by this authorM.-F. Blachon MD, M.-F. Blachon MD Fédération et Pharmacologie Clinique et Médicale et de Pharmacocinétique, MarseilleSearch for more papers by this authorR. Favre MD PhD, R. Favre MD PhD Service d'Oncologie Médicale, La Timone University Hospital, Marseille, FranceSearch for more papers by this authorA. Durand PharmD PhD, A. Durand PharmD PhD Fédération et Pharmacologie Clinique et Médicale et de Pharmacocinétique, MarseilleSearch for more papers by this authorB. Lacarelle PharmD PhD, B. Lacarelle PharmD PhD Fédération et Pharmacologie Clinique et Médicale et de Pharmacocinétique, MarseilleSearch for more papers by this author J. Ciccolini PharmD PhD, J. Ciccolini PharmD PhD Fédération et Pharmacologie Clinique et Médicale et de Pharmacocinétique, MarseilleSearch for more papers by this authorC. Mercier MD, C. Mercier MD Service d'Oncologie Médicale, La Timone University Hospital, Marseille, FranceSearch for more papers by this authorM.-F. Blachon MD, M.-F. Blachon MD Fédération et Pharmacologie Clinique et Médicale et de Pharmacocinétique, MarseilleSearch for more papers by this authorR. Favre MD PhD, R. Favre MD PhD Service d'Oncologie Médicale, La Timone University Hospital, Marseille, FranceSearch for more papers by this authorA. Durand PharmD PhD, A. Durand PharmD PhD Fédération et Pharmacologie Clinique et Médicale et de Pharmacocinétique, MarseilleSearch for more papers by this authorB. Lacarelle PharmD PhD, B. Lacarelle PharmD PhD Fédération et Pharmacologie Clinique et Médicale et de Pharmacocinétique, MarseilleSearch for more papers by this author First published: 20 July 2004 https://doi.org/10.1111/j.1365-2710.2004.00569.xCitations: 62 J. Ciccolini, Fédération de Pharmacologie Clinique et Pharmacocinétique, C.H.U Timone, 235 Rue St Pierre, 13385 Marseille cedex 05, France. Tel: +33 (0)4 91 83 55 09; fax: +33 (0)4 91 83 56 67; e-mail: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Summary Background: Dihydropyrimidine dehydrogenase (DPD) gene polymorphism may lead to severe toxicity with 5-fluorouracil (5-FU), a major anticancer drug extensively used in clinical oncology. Drug monitoring combined with early detection of patients at risk would enable timely dose adaptation so as to maintain drug concentrations within a therapeutic window. However, the best method to identify such patients remains to be determined. Objective: The aim of this study was to develop a rapid and simple high-performance liquid chromatographic (HPLC) method for estimating uracil/dihydrouracil (U/UH2) ratio in plasma, as an index of DPD status, and for assaying 5-FU as part of drug level monitoring. Method: Assay of 5-FU, and U/UH2 detection were performed on a HPLC system equipped with UV detector. Analytes were separated at room temperature using a 5 μm particles, 25 cm RP-18 X-Terra column. The mobile-phase consisted of a KH2PO4 salt solution (0·05 m) + 0·1% triethylamine (TEA) pumped at 0·4 mL/min. Detection of 5-FU and 5-bromouracil were performed at 254 nm; U and UH2 elution was monitored at 210 nm. Results: The method was sensitive and specific for assaying 5-FU within the 5–500 ng/mL concentration range, which covers exposure levels currently met in clinical practice. The method was simple, and relatively cheap, and rapid, with an analytical run time of about 30 min. Data from a patient with 5-FU toxicity suggest that the method was capable of identifying DPD metabolic phenotype in cancer patients, based on measurement of plasma U/UH2 ratio. Conclusion: The method described should be suitable both for detecting patients at high risk of 5-FU toxicity, and for drug level monitoring during chemotherapy. Citing Literature Volume29, Issue4August 2004Pages 307-315 RelatedInformation