Catalytic voltammetric determination of cladribine in biological samples

An electrochemical method for the citotoxic prodrug cladribine determination is proposed. Graphite electrodes modified with cladribine showed a redox process with a formal potential of 0.173 V at pH 6, after the oxidation of the adenine moiety of the drug, whose current can be employed as analytical signal with a detection limit of 75 nM by square-wave voltammetry. As these oxidation products exhibit great electrocatalytic activity toward the electrooxidation of NADH at low potentials, the analytical response can further be amplified. As a result, the detection limit was improved up to 1 nM using differential pulse voltammetry. The method was applied to the determination of cladribine in serum and urine samples after solid-phase extraction. No electroactive interferences were found in both fluids. The method allows the selective detection of the drug in the presence of the main metabolite, 2-chloroadenosine, which is not able to electrocatalize the NADH oxidation.