Valproate–selective potentiometric biosensor: its applications in biological and pharmaceutical samples

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, and requires lifelong anti–epileptic use in some cases. Therefore, the effectiveness of the selected anti–epileptic treatment and its monitoring in the blood during its use is highly important. Valproic acid is one of the most effective and broad–spectrum anti–epileptic drugs used in the epilepsy treatment, and its therapeutic concentration range in the blood is 50–100 µg/mL. In this thesis study, an all–solid–state contact poly(vinyl chloride) (PVC) membrane potentiometry–based biosensor was developed for the determination of valproic acid in human blood samples using γ–aminobutyric acid (GABA) as a bioactive component. In order to identify the optimal percentage of membrane components, biosensors with different ratios of GABA were prepared and their potentiometric performance characteristics were investigated. Based on potentiometric performance properties such as linear working range and limit of detection, the optimum membrane composition was determined as 6.0% GABA, 60.0% o–nitrophenyloctylether (o–NPOE), 32.0 % PVC and potassium tetrakis (p–chlorophenyl) borate (KTpClPB). The valproate–selective biosensor exhibits a Nernstian response for valproate ion over a wide concentration range of 1.0×10−6 – 1.0×10−1 mol L-1 with the slope of 59.0 ± 3.6 mV/decade, and a lower limit of detection of 9.75×10−7 mol L-1. In addition, it was determined that the prepared valproate–selective biosensor showed potentiometric behavior with high reproducibility and it could work unaffected by the changes in pH at pH values ranging from pH 4.0 to 11.0, and had a response time of less than 10 seconds. Finally, using the developed valproate–selective biosensor, valproate determination in biological and pharmaceutical samples was performed with very high recoveries.