Electrochemical oxidation of sildenafil citrate (Viagra) on carbon electrodes

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.     

Diamond paste-based electrodes for determination of Cr(III) in pharmaceutical compounds

A new class of monocrystalline diamond paste-based electrodes is proposed for the determination of chromium(III) at trace levels in vitamins. Three types of monocrystalline diamond—natural diamond 1 (natural diamond), synthetic diamond 50 (synthetic-1), and synthetic diamond 1 (synthetic-2)—were used for electrode construction. The linear concentration ranges are between 10^–10 and 10^–8; 10^–9 and 10^–7, and 10^–10 to 10^–8 mol L^–1, with limits of detection of 10^–12, 10^–12, and 10^–11 mol L^–1, when natural diamond, synthetic-1, and synthetic-2, respectively, are used as electrode materials. For electrodes based on natural diamond and synthetic-1 it was found that Cr(III) yields a peak at about +0.275±0.015 V (vs. Ag/AgCl) within a predetermined positive potential range situated between +0.4 and +0.2 V, while for the electrode based on synthetic-2 the peaks are found at +0.300±0.015 V (vs. Ag/AgCl). The proposed method is reliable for the determination of chromium(III) at trace levels in two vitamin tablets (RSD<0.2%).     

Polymer membrane sensors for sildenafil citrate (Viagra) determination in pharmaceutical preparations

The construction and performance characteristics of ion selective membrane electrodes for sildenafil citrate (SC) drug (the active component of Viagra) are described. The proposed sensors are based on the formation of the complex ion associates of SC with sodium tetraphenylborate (SC-TPB) and phosphomolybdic acid (SC-PMA) as ionophores in poly vinyl chloride membrane (PVC). Both electrodes SC-PMA and SC-TPB showed a linear and stable potential response with near-Nernstian slope of 55.5±0.35 and 53.5±0.3 mV per decade over a wide range of concentration 10⁻² to 10⁻⁵ M sildenafil with good reproducibility, respectively. The electrodes showed a fast response time of 30 and 40 s. and were used over a wide range of pH 3-6. The selectivity coefficients indicated good selectivity for SC drug over a large number of nitrogenous compounds and some inorganic cations. The proposed sensors are tested for the analysis of SC in pure form, pharmaceutical preparations and blood serum. An average recovery of 98.9-99.5±0.6% and correlation to the existing methods of 0.998 were achieved.     

Extractive spectrophotometric methods for the assay of sildenafil citrate (Viagra) in pure form and in pharmaceutical formulations

Two simple and sensitive extractive spectrophotometric methods for the determination of sildenafil citrate (SC) are proposed. The methods are based on the formation of ion-association complexes of sildenafil citrate with bromocresol green (BCG, method A) and with chromoxane cyanine R (CCR, method B) in aqueous acidic buffer. The complex species, extractable to chloroform phase, were quantitatively measured at 415 and 460 nm for methods A and B, respectively. Beer's law was obeyed in the SC concentration range 1.25-25 mug ml(-1) with a limit of detection 0.16 mug ml(-1) and 1.5-60 mug ml(-1) with a limit of detection 0.18 mug ml(-1), respectively, for methods A and B. The methods have been successfully applied to the analysis of bulk drug and its tablets. No interference was observed from common pharmaceutical adjuvants.     

光度法测定枸橼酸西地那非及尿中西地那非的含量

枸橼酸西地那非(Sildenafil citrate)商品名为万艾可(Viagra),是治疗男性性功能障碍药。目前测定西地那非含量的方法主要是HPLC,操作繁琐,仪器昂贵。本文在pH2．5-4．7的酸性介质中,发现乙基曙红(EE)与西地那非(SD)反应后,生成红色离子缔合物,其最大显色波长和最大褪色波长分别为550nm和520nm,表观摩尔吸光     

Separation and determination of synthetic impurities of sildenafil (Viagra) by reversed-phase high-performance liquid chromatography.

A simple and rapid high-performance liquid chromatographic method for the separation and determination of process-related impurities of sildenafil was developed. The separation was achieved on a reversed-phase C18 column using acetonitrile-0.05 M potassium dihydrogen orthophosphate (70:30 v/v) as a mobile solvent at a flow rate of 1.0 ml/min and UV detection at 230 nm. The method was used not only for quality assurance, but also for monitoring the chemical reactions during the synthesis of sildenafil. It was found to be specific, precise and reliable for the determination of all process-related impurities of sildenafil in bulk drugs and formulations.     

Diamond paste based electrodes for the determination of Pb(II) at trace concentration levels

Three types of monocrystalline diamond: natural diamond 1 μm, synthetic diamond 50 μm (synthetic-1), and synthetic diamond 1 μm (synthetic-2) were used for electrodes’ construction. The linear concentration ranges recorded for Pb(II), when natural diamond, synthetic-1 and synthetic-2 based electrodes were used were between 10⁻⁹ and 10⁻⁶; 10⁻¹⁰ and 10⁻⁷; and between 10⁻¹⁰ and 10⁻⁸ mol l⁻¹, respectively. Low detection limits which lie between 10 and 100 pmol l⁻¹ proves the sensitivity of the electrodes. It was found that Pb(II) yielded a peak at about +0.3±0.02 V (versus Ag/AgCl) for all the electrodes. Lead was determine with high reliability from water and tea samples at trace concentration levels using the proposed diamond paste based electrodes.     

Sildenafil citrate (Viagra) as a corrosion inhibitor for carbon steel in hydrochloric acid solutions

Abstract  

The inhibition effect of sildenafil citrate (Viagra) on the corrosion of carbon steel in 1 M HCl was studied by weight loss, polarization, electrochemical impedance spectroscopy, and UV–Vis spectrophotometry. The results showed that sildenafil citrate is a good corrosion inhibitor for carbon steel in acidic media and acts as mixed type (cathodic/anodic) inhibitor. The adsorption of the inhibitor was well described by the Langmuir adsorption isotherm. Some thermodynamic parameters such as adsorption heat, adsorption entropy, and adsorption free energy were calculated. Kinetic parameters such as the apparent activation energy and pre-exponential factor were calculated and discussed.     

Resonance Rayleigh-scattering method for the determination of sildenafil citrate in a pharmaceutical formulation using Evans blue.

A highly sensitive resonance Rayleigh-scattering (RRS) method for the determination of sildenafil citrate has been developed, based on the fact that sildenafil (Sild) reacted with Evans Blue (EB) to form an ion-association complex in pH 1.1 - 4.6 aqueous solution. This resulted in a significant enhancement of the RRS intensity, and a new spectrum appeared. The wavelength of the maximum RRS was at 365 nm, and other scattering peaks were at 400, 442, 470 and 534 nm, respectively. The intensity of RRS was directly proportional to the concentration of Sild in the range 0 - 11.5 microg ml(-1), and the detection limit for Sild (3 sigma) was 30.3 ng ml(-1). The composition of the ion-association complex was Sild:EB = 1:1, as established by Job's method. The method had good selectivity and could be applied to the determination of Sild in the aqueous phase without using organic solvent extraction. The method was simple and rapid. In addition, the reaction mechanism and the reason for RRS enhancement were considered.     

Solid-state ion-selective electrodes for the potentiometric determination of hexacyanoferrate (II)

Hexacyanoferrate(II)-sensing electrodes were prepared by mixing Ag₂S and Ag₄Fe (CN)₆. The 6:1 Ag₂S/Ag₄Fe (CN)₆ provided the best potentiometric response and speed of response. The log concentration vs. potential curves were linear with Nernstian slope (14.8 mV/decade) over the range 10^?1-10^?6 M hexacyanoferrate (II) at pH 7.00 with constant ionic strength. Interferences included iodide, sulfide and bromide. This electrode was used as indicator in potentiometric titrations of hexacyanoferrate (II).     

Determination of sildenafil citrate (viagra) and its metabolite (UK-103,320) by square-wave and adsorptive stripping square-wave voltammetry. Total determination in biological samples

The voltammetric behaviour of Sildenafil citrate (SC) and its main metabolite UK-103,320 (UK) was studied by square wave techniques, leading to two methods for its total determination in biological samples (urine and human serum). The application of the square wave (SW), without the adsorptive accumulation, shows a maximum response at −0.950 V. The effect of experimental parameters that affect this determination are discussed. The stripping technique, proved to be more sensitive, yielding signals three times larger than those obtained by applying a square wave scan without the previous accumulation. Two calibration graphs to determine total SC and UK concentration were established. Calibration graph in urine sample was linear in the range 4.4×10⁻⁸ to 4.8×10⁻⁷ M by the stripping mode with an accumulation time of 10 s. In the same conditions but in serum sample regression line was linear in the range 3.4×10⁻⁸ to 9.7×10⁻⁷ M. The two proposed methods (SW and square-wave adsorptive stripping voltammetry (SWAdSV)) were applied to the total concentration analysis in eight different biological samples by the standard addition method with satisfactory results in the four different serum samples by the SW and in the four urines by SWAdSV.     

Identification of phototransformation products of sildenafil (Viagra) and its N‐demethylated human metabolite under simulated sunlight

Recent publications on pharmaceutical monitoring are increasingly covering the field of illicit drugs and lately the forensic evaluation of designing illegal analogs of lifestyle drugs like the phosphodiesterase type 5 (PDE‐5) inhibitors Viagra (sildenafil), Levitra (vardenafil) and Cialis (tadalafil). Recently, the presence of all three erectile dysfunction treatment drugs has been reported in wastewaters at very low concentrations. In the environment, contaminants undergo various physical or chemical processes classified into abiotic (photolysis, hydrolysis) and biotic (biodegradation) reactions. Thus, changes in the chemical structure lead to the formation of new transformation products, which may persist in the environment or be further degraded. This study describes the photolysis of sildenafil (SDF) and its human metabolite N‐demethylsildenafil (DM‐SDF) under simulated solar radiation (Xenon lamp). Following chromatographic separation of the irradiated samples, eight photoproducts in the SDF samples and six photoproducts for DM‐SDF were detected and characterized. The combination of ultra performance liquid chromatography‐electrospray ionization‐quadrupole time‐of‐flight‐mass spectrometry (UPLC‐ESI‐QToF‐MS), liquid chromatography‐atmospheric pressure chemical ionization‐triple quadrupole mass spectrometry (LC‐APCI‐QqQ‐MS) and hydrogen/deuterium‐exchange experiments allowed to propose plausible chemical structures for the photoproducts, taking into account the characteristic fragmentation patterns and the accurate mass measurements. These mass spectral data provided sound evidence for the susceptibility of the piperazine ring toward photodegradation. A gradual breakdown of this heterocyclic structure gave rise to a series of products, which in part were identical for SDF and DM‐SDF. The sulfonic acid, as the formal product of sulfonamide hydrolysis, was identified as key intermediate in the photolysis pathway. In both drug/metabolite molecules, phototransformation processes taking place beyond the sulfonamide group were deemed to be of minor relevance. Copyright © 2012 John Wiley & Sons, Ltd.     

Micellar electrokinetic capillary chromatography for the determination of Viagra and its metabolite (UK-103,320) in human serum

Micellar electrokinetic capillary chromatography (MEKC) was investigated for the determination of Viagra (sildenafil citrate, SC) and its metabolite (UK-103,320) in human serum in a concentration range of clinical interest. For MEKC, human serum samples spiked with SC and UK were obtained directly after elution with methanol from a tC18 cartridge. The extract was evaporated and regenerated in a solution 1 mM of phosphate buffer (pH 12.3) which contained a methanol percentage of 20% that was analyzed using phosphate buffer (pH 12.3, 10 mM) containing 30 mM sodium dodecyl sulfate (SDS) as separation electrolyte and a fused-silica capillary. This method gave satisfactory interday precision with respect to migration times relative standard deviation (RSD < 1%) and linear responses for the concentration ranges investigated (0.50-3.50 mg L(-1) for the compound SC and 0.90-4.60 mg L(-1) for UK). An intraday RSD (n = 5 graphs) between the slopes of the calibration graphs was acceptable (6.40%) for SC and (3.37%) for UK. A satisfactory interday precision between slopes was also obtained (RSD 4.10% for SC and a RSD 2.72% for UK) which demonstrated the ruggedness of this method. Detection limits (S/N = 3) were about 200 ng/mL for both compounds in human serum. MEKC was shown as a good method with regards to simplicity, precision and sensitivity.     

Spectrophotometric methods for the determination of tamoxifen citrate

Three simple and sensitive spectrophotometric methods for the determination of tamoxifen citrate have been developed. They are based on the formation of an ion-association complex between the drug and a dye, Erioglaucine A, which is extractable into chloroform and has an absorption maximum at 625 nm (method A), oxidation with excess potassium permanganate and the determination of unconsumed permanganate using Fast Green FCF (method B), or by the formation of a coloured cobalt thiocyante coordination complex which is extracted into benzene and measured at 635 nm (method C). Beer's law limits for methods A, B, and C are 0.5-3.0 mug ml(-1), 1.0-6.0 mug ml(-1) and 100-500 mug ml(-1), respectively. No interference was observed from tableting additives and the applicability of the methods was examined by analysing tablets containing tamoxifen. The quantities determined were 99.0-100.03% of the exptected values.     

Spectrophotometric determination of sildenafil citrate in pure form and in pharmaceutical formulation using some chromotropic acid azo dyes

Two simple and highly sensitive spectrophotometric methods were developed for the quantitative determination of the drug sildenafil citrate (SC), Viagra, in pure form and in pharmaceutical formulations, through ion-associate formation reactions (method A) with mono-chromotropic acid azo dyes, chromotrope 2B (I) and chromotrope 2R (II) and ion-pair reactions (method B) with bi-chromotropic acid azo dyes, 3-phenylazo-6-o-carboxyphenylazo-chromotropic acid (III), bis-3,6-(o-hydroxyphenylazo)-chromotropic acid (IV), bis-3,6-(p-N,N-dimethylphenylazo)-chromotropic acid (V) and 3-phenylazo-6-o-hydroxyphenylazo-chromotorpic acid (VI). The reaction products, extractable in methylene chloride, were quantitatively measured at 540, 520, 540, 570, 600 and 575 nm using reagents, I–VI, respectively. The reaction conditions were studied and optimized. Beer's plots were linear in the concentration ranges 3.3–87.0, 3.3–96.0, 5.0–115.0, 2.5–125.0, 8.3–166.7 and 0.8–15.0 μg mL^?1 with corresponding molar absorptivities 1.02 × 10⁴, 8.34 × 10³, 6.86 × 10³, 5.42 × 10³, 3.35 × 10³ and 2.32 × 10⁴ L mol^?1 cm^?1 using reagents I–VI, respectively. The limits of detection and Sandell's sensitivities were calculated. The methods were successfully applied to the analysis of commercial tablets (Vigoran) and the recovery study reveals that there is no interference from the common excipients that are present in tablets. Statistical comparison of the results was performed with regard to accuracy and precision using Student's t- and F-tests at 95% confidence level. There is no significant difference between the reported and proposed methods with regard to accuracy and precision.     

Membrane electrodes for the determination of glutathione

Four glutathione (GSH)-selective electrodes were developed with different techniques and in different polymeric matrices. Precipitation-based technique with bathophenanthroline-ferrous as cationic exchanger in polyvinyl chloride (PVC) matrix was used for sensor 1 fabrication. β-Cyclodextrin (β-CD)-based technique with either tetrakis(4-chlorophenyl)borate (TpClPB) or bathophenanthroline-ferrous as fixed anionic and cationic sites in PVC matrix was used for fabrication of sensors 2 and 3, respectively.β-CD-based technique with TpClPB as fixed anionic site in polyurethane (Tecoflex) matrix was used for sensor 4 fabrication. Linear responses of 1 × 10⁻⁵ to 1 × 10⁻⁴ M and 1 × 10⁻⁶ to 1 × 10⁻³ M with slopes of 37.5 and 32.0 mV/decade within pH 7-8 were obtained by using electrodes 1 and 3, respectively. On the other hand, linear responses of 1 × 10⁻⁵ to 1 × 10⁻² and 1 × 10⁻⁵ to 1 × 10⁻³ M with slopes of 47.9 and 54.3 mV/decade within pH 5-6 were obtained by using electrodes 2 and 4, respectively. The percentage recoveries for determination of GSH by the four proposed GSH-selective electrodes were 100 ± 1, 100.5 ± 0.7, 100 ± 1 and 99.0 ± 0.8% for sensors 1, 2, 3 and 4, respectively. Determination of GSH in capsules by the proposed electrodes revealed their applicability for determination of GSH in its pharmaceutical formulations. Also, they were used to determine GSH selectively in presence of its oxidized form (GSSG). Sensor 4 was successfully applied for determination of glutathione in plasma with average recovery of 100.4 ± 1.11%. The proposed method was compared with a reported one. No significant difference for both accuracy and precision was observed.     

Neutral carriers based polymeric membrane electrodes for selective determination of mercury (II)

The potentiometric response characteristics of mercury ion-selective membrane electrodes based on 2-amino-6-purinethiol (I₁) and 5-amino-1, 3, 4-thiadiazole-2-thiol (I₂) were described. Ion selectivities were tested for various plasticizers, which were used as solvent mediators to incorporate the ionophores into the membrane. Effects of experimental parameters such as membrane composition, nature and amount of plasticizers and additives, pH and concentration of internal solution on the potential response of Hg²⁺ electrodes were investigated. The best performance was obtained with the electrode having a membrane composition (w/w) of (I₁) (3.17%): PVC (31.7%): DOP (dioctylpthalate) (63.4%): NaTPB (sodium tetraphenylborate) (1.58%). The proposed electrode reveals a Nernstian response over Hg²⁺ ion in the concentration range of 7.0 × 10⁻⁸-1.0 × 10⁻¹ M with limit of detection 4.4 × 10⁻⁸ M. The electrode shows good discrimination toward Hg²⁺ ion with respect to most common cations. It shows a short response time (10 s) for whole concentration range and can be used for 2 months without any considerable divergence in potentials. For evaluation of the analytical applicability, the electrode was used in the determination of Hg²⁺ ion in different environmental and biological samples. The practical utility of the membrane electrode has also been observed in the presence of surfactants.     

Improvement of enzyme carbon paste-based biosensor using carbon nanotubes for determination of water-soluble analogue of vitamin E

The catalytic oxidation of a synthetic water-soluble analogue of vitamin E (α-tocopherol, Trolox) by tyrosinase enzyme in the presence of molecular oxygen was studied using electrochemical techniques. This specific enzymatic reaction was exploited for the preparation of a biosensor based on the amperometric reduction of the electroactive product (α-tocoquinone) formed. An electroactive surface of the transducers used was covered with a thin conductive layer of Nafion containing tyrosinase. Significant progress in sensitivity towards polyphenolic compounds such as Trolox was achieved at CPE with carbon nanotubes immobilised on its surface (CPE/CNTs) as electric transducers. The biosensor so developed can be used for the direct determination of total phenolic content (TPC). This important nutrition value can be expressed as the mass equivalent of Trolox, i.e. Trolox equivalent antioxidant capacity (TEAC), which could be used as an alternative to the evaluations currently used based on spectrophotometric methods such as total radical-trapping antioxidant parameter (TRAP), ferric reducing-antioxidant power (FRAP) or 1,1-diphenyl-2-picrylhydrazyl spectrometric assay (DPPH). The effects of the enzyme amount in the Nafion layer (3.0 µg), the influence of the nanoparticles present, the optimal pH value suitable for enzymatic activity (7.0), and the kinetics of enzymatic and electrochemical reactions were studied using cyclic voltammetry (CV). The determination of optimal conditions for amperometry in batch configuration (working potential, speed of stirring, volume of sample, calibration curve, etc.) was not a target of this electrochemical study.