4-sulfophenylmethallyl-ether and Dihydropyrimidine-Dehydrogenase-Deficiency

Main inborn errors of metabolism diagnosable through uracil (Ura) analysis and the therapeutic monitoring of toxic 5-fluorouracil (5FU) in dihydro pyrimidine dehydrogenase (DPD) deficient patients require a sensitive, reproducible, selective and accurate method. In this work, an artificial receptor in the format of molecularly imprinted polymer (MIP) brush 'grafted to' the surface of sol-gel immobilized on cost-effective homemade solid-phase microextraction (SPME) fibers, individually imprinted with either of Ura and 5FU, was used in combination with a voltammetric sensor duly modified with the same MIP. This combination provided up to 10- and 8.4-fold preconcentrations of Ura and 5FU, respectively, which was more than sufficient for achieving stringent detection limits in the primitive diagnosis of uracil disorders and fluoropyrimidine toxicity in DPD-deficient patients. The proposed method permits the assessment of Ura and 5FU plasma concentrations with detection limits pf 0.0245 and 0.0484 ng mL(-1) (RSD = 1.0-2.5%, S/N = 3), respectively, without any problems of non-specific false-positives and cross-reactivities in complicated matrices of biological samples.

Topics: Benzenesulfonates; Binding Sites; Dihydropyrimidine Dehydrogenase Deficiency; Fluorouracil; Humans; Microscopy, Electron, Scanning; Molecular Imprinting; Polymers; Sensitivity and Specificity; Solid Phase Microextraction; Solvents; Spectroscopy, Fourier Transform Infrared; Surface Properties; Uracil