title: Validation of a simple assay for the quantification of the capecitabine metabolites 5'-DFCR and 5'-DFUR for drug monitoring in patients receiving outpatient chemotherapy.
abstract: A simple and precise analytical method for the determination of 5'deoxy-5-fluorocytidine (DFCR) and 5'deoxy-5-fluorouridine (DFUR), the enzymatically formed metabolites of capecitabine in plasma, was developed using a reversed-phase high performance liquid chromatography gradient method with external standard method. Blood samples were analyzed after separation of DFCR/DFUR by solid-phase extraction from matrix compounds using a C16 amide reversed-phase column operated at a flow rate of 0.8 ml/min in gradient elution mode with a mobile phase composed of water-methanol (10 mM ammonium acetate in water; m/v). Excellent recoveries in plasma ranging from 77.5-99.12% for DFCR and 84.70-99.15% for DFUR, respectively, were obtained. For both compounds the calibration curves were linear over the range from 0.156 to 5.0 μg/ml. The present assay is robust, selective and sensitive, and is being applied in our laboratories to monitor plasma concentrations of DFCR and DFUR in clinical phase I and phase II studies.
authors.affiliation: Department of Clinical Pharmacy and Diagnostics, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria. philipp.buchner@univie.ac.at
authors.forename: Philipp
authors.initials: P
authors.lastname: Buchner
authors.forename: Eva
authors.initials: E
authors.lastname: Mihola
authors.forename: Azra
authors.initials: A
authors.lastname: Sahmanovic
authors.forename: Tanja
authors.initials: T
authors.lastname: Steininger
authors.forename: Christian
authors.initials: C
authors.lastname: Dittrich
authors.forename: Martin
authors.initials: M
authors.lastname: Czejka
mesh_terms: D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000097:blood; D016903:Drug Monitoring / Q000379:methods*; D004355:Drug Stability; D005467:Floxuridine / Q000031:analogs & derivatives* / Q000097:blood; D006801:Humans; D057230:Limit of Detection; D010045:Outpatients; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction
chemical_list: D005467:Floxuridine; D003841:Deoxycytidine; C418208:5'-deoxy-5-fluorocytidine; C025034:doxifluridine