Voltammetric behavior of sildenafil citrate (Viagra) using square wave and adsorptive stripping square wave techniques: Determination in pharmaceutical products
Introduction
Viagra, an oral therapy for erectile dysfunction, is the citrate salt of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase Type 5 (PDE5).
Sildenafil citrate is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1-H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine citrate (structural formula in Fig. 1).
The physiological mechanism of erection of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme, guanylate cyclase, which results in increased levels of cGMP, producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood.
SC is a novel oral agent under development for the treatment of penile erectile dysfunction. It is a potent and selective inhibitor of 5-cyclic GMP-specific phosphodiesterase [1], [2].
The effects of SC on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes was determined by Ballard et al. [3].
Osterloh and co-workers [4] determined the efficacy and safety of fixed-dose oral sildenafil in the treatment of erectile dysfunction of various etiologies. The sildenafil was a very effective and well tolerated treatment for the erectile dysfunction.
SC is rapidly absorbed after oral administration, with absolute bioavailability of about 40%. Its pharmacokinetics are dose-proportional over the recommended dose range. It is eliminated predominantly by hepatic metabolism and is converted to an active metabolite with properties similar to the parent, sildenafil. Both sildenafil and the metabolite have terminal half lives of about 4 h.
An isocratic HPLC method [5] using acetonitrile–phosphate buffer–water (28:4:68 v/v/v) with detection at 230 nm was utilised as routine analysis of SC in pharmaceutical products. In this paper, it has also been proposed as a procedure for the simultaneous determination of sildenafil and its metabolite (UK-103,320) using automated sequential trace enrichment of dialysates (ASTED) and HPLC.
Adsorptive stripping voltammetry (AdSV) has been demonstrated to be a useful technique for the study and determination of many molecules of biological importance [6]. The high sensitivity of adsorptive stripping methods is obviously their greatest advantage. If the sample contains interesting compounds that are electrochemically active but are not absorbed on the electrode surface, then classical separation procedures are not necessary. Another advantage is the possibility of working with very diluted samples with the corresponding decrease in interference in pharmaceutical analysis.
This paper shows that the SC compound is a drug, which suffers a strong absorption process onto a mercury electrode. By using this phenomenon and by accumulation of this compound at hanging mercury dropping electrode (HMDE) prior to square wave voltammetric measurement, higher sensitivities can be readily achieved. The influence of several experimental (pH, ionic strength) and instrumental (step increment, pulse amplitude, frequency, drop size) variables on the square wave and on the stripping square wave response has been evaluated. The proposed method was applied in the determination of SC in presence of other components (excipients) in three different presentations of the same product Viagra (25, 50 and 100 mg).
Section snippets
Materials
All solvents and reagents were of analytical reagent grade unless indicated otherwise. Solutions for voltammetric study were made with deionized water (Milli-Q quality). Stock solutions of 0.011 M HClO4 were prepared using suprapure grade reagent.
Sildenafil citrate was obtained from Pfizer. Standard solutions (16.0 mg/l) were prepared in water and stored at 4°C. Their stability was evaluated over a period of 15 days by electrochemistry. Diluted solutions of SC were prepared daily in water.
Apparatus
Results and discussion
The preconcentration of SC at the HMDE and the application of a subsequent differential pulse voltammetric (DPV) scan in the negative direction gave rise to two stripping reduction peaks (Ep=−0.95 and −1.020 V) at pH 2.0 (HClO4) (Fig. 2). As seen in Fig. 2, a large response is obtained only after 30 s of accumulation time for an assayed concentration of 5.0×10−7 M of the drug. On the contrary, the solution phase response (direct response, tacc=0 s) shows a very small reduction peak as expected for
Conclusions
This work shows that the SC can be determined using voltammetric techniques on the basis of its reduction process over the hanging mercury drop electrode. This behaviour provides a useful tool for its detection and quantification at low levels of concentration.
A faster analysis can be performed by direct measurement from the calibration graph established for SW. This method is sensitive enough, the accumulation time is removed and there are no interference in the analysis from the other
Acknowledgements
The authors wish to thank Pfizer Spain (Medical Division) and Pfizer Central Research for their help in the research sample contribution of sildenafil citrate and also to the DGES of the Ministerio de Educación y Ciencia of Spain for the financial support (Project PB-97-0431).
References (7)
- et al.
J. Urol.
(1998) - et al.
Urology
(1999) - et al.
J. Chromatogr. B
(1997)
Cited by (58)
Screen-printed sensor for determination of sildenafil citrate in pharmaceutical preparations and biological samples
2019, Microchemical JournalCitation Excerpt :In order to increase the sensitivity of the analysis, various types of working electrodes are used. Literature sources describe the determination of sildenafil citrate at the hanging mercury drop electrode [8,9]. Many methods have also been developed using carbon electrodes, including glassy carbon electrodes, glassy carbon electrode modified with lead film, pencil graphite electrode, diamond paste electrode and boron doped diamond electrode [7,10–14].
A new magnetic nanodiamond/graphene oxide hybrid (Fe<inf>3</inf>O<inf>4</inf>@ND@GO) material for pre-concentration and sensitive determination of sildenafil in alleged herbal aphrodisiacs by HPLC-DAD system
2018, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life SciencesElectrochemical determination of sildenafil citrate as standard, in tablets and spiked with human serum at gold and cystein modified gold electrode
2016, Journal of Electroanalytical ChemistryBismuth film electrode for stripping voltammetric measurement of sildenafil citrate
2012, Electrochimica ActaCitation Excerpt :On the other hand, electrochemical techniques offer an attractive approach for direct, fast, simple and inexpensive measurements of electroactive organic and inorganic species, particularly in combination with stripping protocols which enable unique pre-concentration of the analyte in/on the surface of the selected working electrode. Hence, in the last few years, several attempts were taken to measure SC electrochemically using different types of electrodes and methods, e.g. SC was voltammetrically oxidized at boron-doped diamond electrode [11,12] and at glassy carbon electrode [13], reduced at hanging mercury drop electrode [14,15] and at the in situ prepared lead film electrode [16], and measured with electrochemical DNA biosensor [17]. Among these electrode materials, lead and mercury are well-known as toxic heavy metal pollutants being the latter associated also with significant difficulties in its handling, disposal, and subjected to very strict regulations.
Electroanalytical determination of sildenafil in Viagra tablets using screen-printed and conventional carbon paste electrodes
2011, Journal of Electroanalytical ChemistryCitation Excerpt :No official (pharmacopoeial) method has been found for the assay of SILC in its formulations. Reports have been appeared describing accurate spectrochemical and chromatographic techniques for quantification and stability assay of SILC [2–12]. Most of these methods are expensive, suffer from lack of selectivity and require careful control of conditions and considerable time for routine control analysis [7,8].
Strategically functionalized carbon nanotubes as the ultrasensitive electrochemical probe for picomolar detection of sildenafil citrate (Viagra)
2011, Biosensors and BioelectronicsCitation Excerpt :The cathodic peak current at +0.72 V (under optimum conditions, Supporting information S1) showed linearity for a wider concentration range of SC (1 × 10−11 to 0.896 × 10−4 M (R2 = 0.9978, n = 7)) (Fig. 4, inset). The linear concentration range (1 × 10−11 to 0.896 × 10−4 M) for SC is much wider than reported in literature (Ozkan et al., 2004; Nevado et al., 2001; Altiokka et al., 2001; Dinesh et al., 2002; Berzas et al., 2000; Liu et al., 2006; Rauf et al., 2007) (Table 1). The limit of detection (LOD) and limit of quantification (LOQ) for SC at MWNT-g-PABS electrode are 0.469 × 10−11 M and 1.563 × 10−11 M, respectively.