Analytica Chimica Acta 501 (2004) 227–233 Electrochemical oxidation of sildenafil citrate (Viagra) on carbon electrodes Sibel A. Özkan a , Bengi Uslu a , Petr Zuman b,∗ a Department of Analytical Chemistry, Faculty of Pharmacy, Ankara University, 06100 Ankara, Turkey b Department of Chemistry, Clarkson University, Potsdam, NY 13699-5810, USA Received 8 May 2003; received in revised form 9 September 2003; accepted 23 September 2003 Abstract In aqueous solutions containing 30% (v/v) acetonitrile the unprotonated form of the piperazine ring of sildenafil (I) is oxidized on a glassy carbon electrode between pH 2 and 8. Whereas citrate anions under conditions used are not oxidized, the oxidation pattern of sulfonamides differs from that of sildenafil (I). On the other hand, the oxidation of I resembles that of the oxidation of piperazine ring in nefazodone (III) and trazodone (IV). A more positive peak of sildenafil corresponds to an adsorption–desorption process. Measurement of the peak current enables rapid determination of sildenafil (I) in pharmaceutical preparations with sufficient accuracy. © 2003 Elsevier B.V. All rights reserved. Keywords: Sildenafil citrate; Oxidation mechanism; Drug analysis; Voltammetry 1. Introduction Viagra, sildenafil citrate (I), which is used to control erec- tile disfunction, is chemically 1-[{3-(6,7-dihydro-1-methyl- 7-oxo-3-propyl-1-H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-etho- xyphenyl} sulfonyl]-methyl piperazine citrate (I). Among methods used for determination of I belong uses of LC, for example, in acetonitrile–water mixture with phos- phate buffer (detection at 230 nm) [1] or at 245 nm [2] or with ammonium acetate (detection at 240 nm) [3]. Alter- native methods used were the micellar electrokinetic chro- ∗ Corresponding author. Tel.: +1-315-268-2389; fax: +1-315-268-6610. E-mail address: zumanp@clarkson.edu (P. Zuman). matography [4,5], spectrophotometry, based on function of ion-pairs of I with dyes which can be extracted [6], or flow- injection analysis with UV detection [7]. Commonly used separation techniques are undoubtedly superior, when I is to be determined in the presence of impurities from manufacture or of metabolites. But it can be questioned, whether such procedures present the fastest, most accurate and most sensitive analytical methods for de- termination of the drug I in pharmaceutical preparations. Under specific circumstances, electrochemical methods can offer optimal solution. Perhaps more than in other an- alytical techniques, to make the best use of electroanalyt- ical procedures, it is essential that both the physical and chemical processes involved in the measured signal are un- derstood. This condition was not fulfilled in the investiga- tion [8] in which the authors proposed a highly sensitive method for determination of compound I. This procedure was based on application of square wave and adsorptive stripping SWV using a hanging mercury drop electrode. The nature of the processes manifested in current peaks observed in solutions of perchloric acid of pH 2 was not identified. Furthermore, in protic solvents where electron transfers are accompanied by proton transfers, the important role of pH was not reported or discussed. Resulting empir- ical analytical method may be prone to unexpected matrix effects. 0003-2670/$ – see front matter © 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.aca.2003.09.033