The electrochemical reduction of the antiretroviral drug, tenofovir (TNF), was studied in Britton Robinson (BR) buffer at the hanging mercury drop electrode (HMDE). Tenofovir showed one well-defined reduction peak in the potential range -1.2 to -1.4 V (vs. Ag/AgCl) due to reduction of the C = N bond of the imidazole ring. A method based on square-wave cathodic adsorptive stripping voltammetry (SWCAdSV) was optimized and validated for assay of TNF in human plasma and a tablet formulation. Sample preparation of plasma involved protein precipitation with acetonitrile. The method was linear in the concentration range 0.5-5.0 mu g/mL in both standard solutions and plasma with lower limits of quantitation (LLOQ) of 0.39 and 0.76 mu g/mL respectively. Accuracy was within the acceptance criteria of 100 +/- 15% of the theoretical value except at the LLOQ where it was 100 +/- 20%. Precision was within the criteria of 15% at all concentration levels. The proposed method was successfully applied to the determination of TNF in human plasma and a tablet formulation. (C) 2013 The Electrochemical Society. All rights reserved.