Available online at www.scholarsresearchlibrary.com Scholars Research Library Der Pharmacia Lettre, 2012, 4 (5):1599-1606 (http://scholarsresearchlibrary.com/archive.html) ISSN 0975-5071 USA CODEN: DPLEB4 1599 Scholar Research Library Electrochemical behaviour and Validated Determination of the Anticancer Drug Tamoxifen D. K. Sharma 1 , G. L. Mourya 1 , K K Jhankal 1 , Lathe A. Jones 2 and Suresh K. Bhargava 2 1 Department of Chemistry, University of Rajasthan, Jaipur-302055, India. 2 School of Applied Sciences, RMIT University, GPO Box 2476V, Melbourne, Australia. _____________________________________________________________________________________________ ABSTRACT The electrooxidative behaviour of tamoxifen (Tam) and 4-hydroxytamoxifen (TamOH) was investigated by cyclic (CV), differential-pulse adsorptive anodic stripping (DPAdAS) and square-wave adsorptive anodic stripping (SWAdAS) voltammetric techniques. The anodic oxidation peak of Tamoxifen was attributed to the cyclization reaction to form the corresponding phenanthrene derivative and the mechanism of oxidation was postulated on the basis of controlled potential electrolysis and isolation of the oxidative product. Oxidative stripping analysis was successfully applied to the determination of tamoxifen in a bulk pharmaceutical formulation, and sensitivity in human urine and serum was validated. The achieved limits of detection (LOD) of bulk tamoxifen were 1.8 × 10 –6 mol L –1 and 2.4 × 10 –6 mol L –1 for DPAdAS and SWAdAS, respectively. The LOD values for tamoxifen in human urine and serum sample analysis were 4.75 × 10 –7 mol L –1 and 2.63 × 10 –7 mol L –1 and 1.98 × 10 –7 mol L –1 and 3.28 × 10 –7 mol L –1 for DPAdAS and SWAdAS, respectively. 4-hydroxytamoxifen is oxidised at more positive potentials than Tamoxifen, separated from the Tamoxifen stripping peak, and its adsorption to the glassy carbon electrode is less pronounced. This affects the ability to determine this important phase I metabolite in serum and urine samples. Key words: tamoxifen; 4-hydroxytamoxifen; anodic adsorptive stripping voltammetry. _____________________________________________________________________________________________ INTRODUCTION Tamoxifen, [Z]-2-[4-(1,2-diphenyl-1-butenyl)-phenoxy]-N,N-dimethylethylamine (Tam), a nonsteroidal anti- estrogen, has been the most important hormonal agent for treatment of breast cancer for more than two decades, and recently has been approved as a long-term chemo preventive agent for breast cancer in healthy women at high risk for developing breast cancer.[1-4] Tamoxifen undergoes chemical transformation to its phase I metabolites in vivo, resulting in a series of modified species, predominately through methylation or hydroxylation of the benzene rings on the tamoxifen structure, to structures such as 4-hydroxytamoxifen.[1] O N