Redox labeling of two antiepileptic drugs with metallocenes and their simultaneous detection by a Nafion-modified electrode

Two different cationic redox labels, i.e. a ferroceneammonium ion and a cobaltocenium ion, were covalently attached to two antiepileptics, phenytoin and phenobarbital, respectively. The two labeled drugs possess distinct standard redox potentials of 0.39 V for the phenytoin derivative and −0.92 V for phenobarbital derivative (vs Ag/AgCl, Cl− 0.05 M) at a carbon paste electrode. After preconcentration in a polyanionic Nafion-loaded carbon paste electrode the positively charged labeled phenytoin and phenobarbital derivatives could be simultaneously detected in concentration ranges which were relevant to the therapeutic ranges of the antiepileptics, with a view to a future dual-analyte immuno- assay. Square-wave voltammetry permitted detection limits of 5×10−8 M (for the phenytoin derivative) and 2.5×10−8 M (for the phenobarbital derivative) for non-simultaneous detection.