Molecular displacement approach for the electrochemical detection of protein-bound propofol

Propofol is one of the principal drugs used for the sedation of patients undergoing mechanical ventilation in intensive care units. The correct dosage of such sedative drugs is highly important, but current methods of determining infusion rates are limited and there is a lack of suitable methods for directly determining patient blood propofol concentrations. A significant challenge for the development of propofol sensors is that propofol demonstrates very high protein binding, leading to a low free fraction in blood. Here we present a method for improving the efficacy of an electrochemical propofol sensor by increasing the free fraction via a molecular displacement approach. When used in conjunction with a carbon nanotube/graphene oxide/iron oxide nanoparticle functionalised screen-printed electrode, it was found that this approach dramatically improved the sensor's sensitivity towards propofol. Ibuprofen was found to be the most effective displacement agent, with an optimal concentration of 30 mM. The resultant sensitivity was 2.82 nA/μg/ml/mm 2 with a coefficient of variation of 0.07, and the limit of detection was 0.2 μg/ml. This approach demonstrates high specificity towards drugs commonly administered to intensive care patients. • High protein binding makes it challenging to detect propofol in serum. • Introducing a displacer molecule can increase unbound propofol. • The performance of an electrochemical propofol sensor is dramatically improved. • Ibuprofen is found to be the optimal displacer molecule for propofol.