Sodium channel inhibition is an established mechanism that can confer anticonvulsant efficacy across a broad spectrum of seizure types [1-3]. However, a quantitative relationship between sodium channel inhibition and clinical anticonvulsant efficacy has yet to be determined. Traditional patch-clamp electrophysiology is the in vitro gold standard for measurement of compound activity on ion channels. However it has limited use for the evaluation of many drugs due to low throughput. The QPatch automated planar array patch-clamp system has been designed to increase throughput. The aim of this study was to develop and validate a robust electrophysiology assay using QPatch to define the interaction of drugs with recombinant human Nav1.2 sodium channels. In particular, to allow estimation of the affinity of drugs for the inactivated state of the channels (Ki). This value could then be used to explore the relationship between drug potency observed in vitro and brain concentration required for efficacy in vivo. A first set of experiments was performed to assess assay fidelity and recording quality. A classic voltage step protocol was applied consisting of depolarising voltage steps (10 ms), increasing by 10 mV from -40mV to +40 mV from a holding potential of -90 mV. The I-V plot obtained suggests that the inward current reverses at around +50 to +60 mV, consistent with the reversal potential of sodium ions observed using a manual patch clamp assay. Secondly, the sensitivity of the QPatch assay to DMSO, used to dissolve test compounds, was assessed. The data obtained suggest that a maximum concentration of 0.3% can be reached without affecting recorded currents. In a further set of experiments the viability of whole cell recordings over time was determined. For these experiments, test pulses to 0 mV were applied at a regular interval. Currents remained stable for at least 20 minutes. Finally, a steady state inactivation protocol was applied to determine the affinity of compounds for the inactivated state (Ki)[4]. HEK-hNav1.2 cells were held at -120 mV and stepped to different conditioning voltages (-120/-40 mV) for 9 s to induce steady state inactivation. At the end of each conditioning period the cell was stepped to +20 mV for 2 ms to elicit sodium current. For each recording, the peak current was plotted against the conditioning voltage and the data fitted to a Boltzmann equation from which the half-maximal inactivation voltage (Vh) could be determined. Application of drug caused a concentration-dependent leftward shift of the inactivation curve. By plotting the shift in Vh against drug concentration it was possible to estimate the Ki of the compound tested. The results show that the QPatch system provides a robust assay that can be used to evaluate the interaction of compounds with recombinant human Nav1.2 sodium channels.