Analytica Chimica Acta 555 (2006) 341–347 Electrooxidation of the antiviral drug valacyclovir and its square-wave and differential pulse voltammetric determination in pharmaceuticals and human biological fluids  Bengi Uslu a , Sibel A. ¨ Ozkan a ,Z¨ uhre S ¸ent¨ urk b,∗ a Faculty of Pharmacy, Department of Analytical Chemistry, Ankara University, 06100 Ankara, Turkey b Faculty of Science and Letters, Department of Chemistry, Y¨ uz¨ unc¨ u Yıl University, 65080 Van, Turkey Received 1 November 2002; received in revised form 3 January 2005; accepted 15 September 2005 Available online 19 October 2005 Abstract The electrochemical properties of valacyclovir, an antiviral drug, were investigated in pH range 1.8–12.0 by cyclic, differential pulse and square- wave voltammetry. The drug was irreversibly oxidized at a glassy carbon electrode in one or two oxidation steps, which are pH-dependent. For analytical purposes, a very resolved diffusion controlled voltammetric peak was obtained in Britton–Robinson buffer at pH 10.0 using differential pulse and square-wave modes. Limits of detection were 1.04 × 10 -7 and 4.60 × 10 -8 M for differential pulse and square-wave voltammetry, respectively. The applicability to direct assays of tablets, spiked human serum and simulated gastric fluid, was described. © 2005 Elsevier B.V. All rights reserved. Keywords: Valacyclovir; Cyclic voltammetry; Differential pulse voltammetry; Square-wave voltammetry; Glassy carbon electrode; Tablet; Biological fluids 1. Introduction Substituted purines represent an important category of com- pounds actively studied as potential therapeutics against viral infection. Because they constitute the essential components of biologically important compounds such as polynucleic acids, and because their electrochemical and enzymatic oxidations follow similar mechanistic pathways, the knowledge of voltam- metric behavior of these compounds is of biological interest [1,2]. It is therefore important to examine the electrochemistry of a recently developed guanine analogue, valacyclovir that is used for the treatment of diseases caused by herpes simplex and varicella zoster virus infections. This compound is converted rapidly and extensively to acyclovir, the active antiviral com- ponent of valacyclovir, and l-valine, an essential amino acid, probably in the liver and the intestine by hydrolysis, after oral administration. Because of the low bioavailability of acyclovir  Presented at Third Aegean Analytical Chemistry Days, Lesvos, Greece, September 29–October 3, 2002. ∗ Corresponding author. Tel.: +90 4322251661; fax: +90 4322251663. E-mail address: zuhre@yyu.edu.tr (Z. S ¸ent¨ urk). (only 15–30% of the dose is absorbed from the gastrointestinal tract), its different esters have been synthesized. One of them is valacyclovir, which is readily absorbed (about 50% of the dose) after oral administration [3]. There have been only few reports dealing with the determi- nation of valacyclovir based on high performance liquid chro- matography [4–6]. These reported methods are not specific for valacyclovir and time-consuming. A revision of the literature has given no evidence about electrochemical studies related to valacyclovir. Consequently, quantitative determination of this drug using electrochemical techniques is a non-explored matter up to day. Since the development of modern computer-based electro- chemical instrumentation, electroanalytical techniques, espe- 0003-2670/$ – see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.aca.2005.09.034