Electrochemical characteristics of zafirlukast and its determination in pharmaceutical formulations by voltammetric methods

Simple, rapid, reliable and fully validated voltammetric methods were developed for the determination of zafirlukast in pharmaceutical formulations, based on its electrochemical reduction at a hanging mercury drop electrode. Its electrochemical behavior in borate buffer (pH 8.0) was investigated using cyclic voltammetry, linear sweep voltammetry and chronoamperometry. The linear sweep voltammetric study of zafirlukast was carried out using glassy carbon electrode. A well-defined cathodic peak at -1326 mV without the adsorptive accumulation time and at -1312 mV with 20 s of accumulation time versus Ag/AgCl reference electrode in square-wave and square-wave adsorptive stripping voltammetric methods, respectively, was observed. The experimental and instrumental parameters affecting the peak current of zafirlukast were investigated and optimized for the zafirlukast determination. The detection limits of square-wave and square-wave adsorptive stripping voltammetric methods were 50 and 5 ngmL(-1) with R.S.D. of 6.79 and 5.72%, respectively. The methods showed good sensitivity, accuracy, precision, selectivity, robustness and ruggedness. The proposed methods were applied for the determination of zafirlukast in its pharmaceutical formulations. The results obtained from developed methods were compared with a spectrophotometric method reported in the literature and no significant difference was found statistically.     

Adsorptive stripping voltammetry of nicardipine at a HMDE; determination of trace levels nicardipine in blood and urine

The redox behaviour of nicardipine, a 1,4-dihydropyridine calcium antagonist, has been studied in different media on mercury, glassy carbon, gold and platinum electrodes using various voltammetric techniques. A highly sensitive adsorptive stripping voltammetric method for the determination of nicardipine based on adsorption of the drug onto mercury, followed by differential pulse voltammetric determination of the surface species, is described. All factors (pH, supporting electrolyte, accumulation potential and time, etc.) influencing adsorption as well as voltammetric response are discussed. The application of adsorptive stripping voltammetry at the hanging mercury drop electrode (HMDE) to the determination of trace levels of nicardipine in human urine and blood is illustrated, without an extraction procedure being necessary prior to the voltammetric measurement. A limit of detection of 4.8 ng per ml urine and 34 ng per ml blood is found with a mean recovery of nicardipine in urine and blood of 97%. The mean relative error does not exceed 6.5%.     

Voltammetric behavior and assay of the antibiotic drug cefazolin sodium in bulk form and pharmaceutical formulation at a mercury electrode

The electrochemical behavior of the antibiotic drug cefazolin sodium (CFZ) in Britton–Robinson buffers (pH 2–11) at the mercury electrode was studied by means of dc-polarography, cyclic voltammetry, controlled-potential coulometry and square-wave adsorptive stripping voltammetry techniques. A validated square-wave adsorptive cathodic stripping voltammetric procedure was described for the trace determination of cefazolin in bulk form up to limits of detection and quantitation of 2.6 × 10⁻¹⁰ M and 8.6 × 10⁻¹⁰ M, respectively. The method was successfully applied for determination of cefazolin in pharmaceutical preparation without the necessity for samples pretreatment or any time-consuming extraction or evaporation steps prior to the analysis.     

Direct determination of metformin in urine by adsorptive catalytic square-wave voltammetry

A new adsorptive catalytic voltammetric method for voltammetric determination of metformin based on the catalytic hydrogen evolution reaction at a hanging mercury drop electrode was developed. The electrode reaction was analyzed under conditions of linear sweep voltammetry (LSV), differential pulse voltammetry (DPV) and Osteryoung-type square-wave voltammetry (SWV). The peak current depends on pH of the medium, concentration and chemical composition of the buffer solution, and instrumental parameters. The optimal conditions for quantitative determination were obtained in an acetate buffer at pH 4.7. The voltammetric procedure was characterized with respect to the repeatability, precision and the recovery. The detection and quantification limits were found to be 1.8 x 10(-8) and 5.9 x 10(-8) mol l(-1) for SWV, 3.2 x 10(-8) and 1.0 x 10(-7) mol l(-1) for DPV, and 7.7 x 10(-8) and 2.5 x 10(-7) mol l(-1) for LSV, respectively. The SW voltammetric method, as the most sensitive one, was applied for determination of metformin in human urine. The voltammetric method has been validated by using HPLC with UV detection.     

Analysis of diflunisal by electrochemical methods

A new differential pulse polarographic (DPP) and differential pulse adsorptive stripping voltammetric (DPAdSV) methods for the electrochemical behavior and quantitative determination of diflunisal were described. In these voltammetric methods, the peak potential of diflunisal was found as -0.31 V (vs. Ag/AgCI) with selected Britton--Robinson buffer (BR, pH 7.8) as a supporting electrolyte. The variation of the peak current with the concentration of diflunisal were linear in the 9.0--40.0 and 4.0--30.0 microg ml(-1) concentration ranges for DPP and DPAdSV methods, respectively. The limits of detection (LOD) were found as 5.0 and 0.1 microg ml(-1) for DPP and DPAdSV methods, respectively. The developed methods were validated by evaluation of the validation parameters. The characteristics of the peak current of diflunisal were examined in detail and the results proved that the peak current has an adsorption characteristic. The developed methods were proposed for rapid determination of diflunisal in commercial tablets. The recovery studies showed that developed assays had a good accuracy and precision with mean recoveries 99.92 and 100.02% and mean variation coefficients 0.29 and 0.24% in DPP and DPAdSV methods, respectively.     

Voltammetric determination of cilazapril in pharmaceutical formulations

A sensitive adsorptive stripping voltammetric method for the measurement of cilazapril in 0.04 M Britton-Robinson buffer (pH 9.0) solution was described. The method was based on the adsorptive accumulation of the drug at a hanging mercury drop electrode (HMDE), followed by differential pulse voltammetry. The response was evaluated with respect to pre-concentration time, pH effect, accumulation potential, accumulation time and scan rate. The peak potential was -0.60 V (vs. Ag/AgCl). The peak current was directly proportional to the concentration of cilazapril with a detection limit of 17.6 ng ml(-1) at an accumulation time of 10 s. The reduction process was irreversible and the wave showed adsorptive characteristics. The results were compared to those obtained using a HPLC procedure. A reversed-phase C18e column with aqueous phosphate buffer (pH 3.5; 0.125 M)-acetonitrile (67:33, v/v) mobile phase and benazapril as internal standard was used. UV detector was set at 254 nm. Results obtained in HPLC were comparable to those obtained by adsorptive stripping voltammetric method.     

Determination of pantoprazole by adsorptive stripping voltammetry at carbon paste electrode

A voltammetric method was described for the determination of pantoprazole by differential-pulse adsorptive stripping voltammetry at a carbon paste electrode. Accumulation of pantoprazole was found to be optimized in Britton-Robinson buffer (0.04 M, pH 4.0) solution following 5 min accumulation time at open circuit condition. Under optimized conditions, the current showed a linear dependence with concentration in the range 1.0 x 10(-7)-1.0 x 10(-5) M. The detection limit was 2.0 x 10(-8) M. The method was applied successfully for the analysis of pantoprazole in tablet dosage form. The results of accuracy and precision were comparable to those obtained by spectrophotometry.     

Determination of the antibacterial trovafloxacin by differential-pulse adsorptive stripping voltammetry

A differential-pulse adsorptive stripping voltammetric method for the determination of trace amounts of the antibacterial trovafloxacin (TRFLX) is proposed. The optimal experimental parameters for the drug assay were: accumulation potential=-0.30 V (vs. Ag/AgCl), accumulation time=120 s, pulse amplitude=50 mV and scan rate=5 mV s(-1) in Britton-Robinson buffer (pH 4.5). The linear concentration range of application was 2.0-20.0 ng ml(-1) of TRFLX, with a relative standard deviation of 3.6% (for a level of 5.0 ng ml(-1)) and a detection limit of 0.6 ng ml(-1). The method was applied to determination of TRFLX in human urine and serum samples. It was validated using HPLC as a reference method. Recovery levels of the method reached 100% in all cases     

Adsorptive stripping voltammetry of trimethoprim: mechanistic studies and application to the fast determination in pharmaceutical suspensions

The adsorptive stripping voltammetric behaviour of trimethoprim (TMP) was studied at pH 3.8 and 7.0 by linear-sweep (LS) and cyclic voltammetry at the hanging mercury drop electrode. The charges and surface concentrations of the protonated TMP species were determined at both pH values. Taking advantage of the adsorption features of TMP fast voltammetric techniques (LS and square-wave (SW) voltammetry) were applied to the determination of TMP at the 10(-7)mol dm(-3) concentration level (pH 3.8). For these concentrations the relative standard deviations were <2% (N=8) and the detection limit was 10nM (3 ng/mL) for the SW-AdCSV (3s; accumulation time 10s, frequency 100 Hz). The use of SW-adsorptive cathodic stripping voltammetry originated a very fast and sensitive method for the direct analysis of TMP in pharmaceutical suspensions without any matrix effects or interference from sulfamethoxazole. No sample pre-treatments or solvent extraction procedures were needed. The quantitative results were in agreement with the data supplied by the manufacturer.     

Applicability of the silver amalgam electrode in voltammetric determination of zinc and copper in gastric juice and gastric mucosa of rats

The aim of the work was to compare two analytical methods of trace analysis in respect to their applicability in heavy metals determination in biological samples. Atomic absorption spectrometry (AAS) may be considered as the method of choice in such analyses due to its accuracy, precision and low detection limit. On the other hand, voltammetric methods seem to be as useful, but rarely applied. Having in mind that there is no universal analytical method, we have compared two AAS and voltammetric methods as the tools for Zn and Cu determination in the samples collected from rat gastric juice and gastric mucosa. Construction of the renewable silver amalgam film electrode (Hg(Ag)FE) for stripping voltammetry was described. Detailed optimization of measurements procedure and sample preparation for differential pulse anodic stripping voltammetry (DP ASV) and AAS were also performed and presented. The obtained results of quantitative analysis of the chosen parameters by means of both methods are discussed.     

Electrochemical behavior of quinapril and its determination in pharmaceutical formulations by square-wave voltammetry at a mercury electrode

The electrochemical behavior of the antihypertensive drug quinapril was investigated at a hanging mercury drop electrode using different voltammetric techniques such as cyclic voltammetry, square-wave voltammetry and chronoamperometry. A simple and sensitive square-wave voltammetric method for the electrochemical analysis of quinapril in its pharmaceutical formulations was developed and validated. The experimental and instrumental parameters affecting the peak current of quinapril were investigated. Various buffers such as Britton Robinson, borate and phosphate buffers at different pH values (3.0-11.0) were examined as supporting electrolyte. The optimum conditions were obtained using Britton Robinson buffer at pH 10.0 and frequency: 50 Hz, scan increment: 4 mV and pulse amplitude: 25 mV. A well-defined peak current was observed at the hanging mercury drop electrode at -1100 mV vs. Ag/AgCl reference electrode. This proposed method was validated by evaluating linearity, sensitivity, repeatability, accuracy, precision, selectivity, recovery, robustness and ruggedness. The linear calibration range was 0.50-8.68 microg mL-' (r = 0.9992). The detection and quantification limits of this method were 0.22 and 0.50 Ctg mL(-1) and intra-day and inter-day precision were between 0.81-4.32% (n = 7), respectively. The developed method was applied successfully for the determination of quinapril in its tablet dosage forms. The average amount of quinapril in tablets was found as 20.26 +/- 0.12 with RSD of 1.60% for 20 mg tabletsand 40.55 +/- 0.23 with RSD of 1.52% for 40 mg tablets.     

Electroanalytical study of the antidepressant sertraline

A flow injection square wave cathodic stripping voltammetric method has been developed for the determination of sertraline in a pharmaceutical preparation. The method shows linearity between peak current intensity and sertraline concentration for the interval between 0.20 x 10(-6) and 1.20 x 10(-6) mol L(-1). Limits of detection and quantification were found to be 1.5 x 10(-7) and 5.0 x 10 (-7) mol L(-1), respectively. Up to 70 samples per hour can be analysed with a good precision (R.S.D. = 2.5%). The proposed method was successfully applied to the determination of sertraline in a commercial product. In the voltammetric determination of sertraline in flow, a high sample rate is obtained at reduced costs, opening the possibility to compete with the chromatographic methods generally used for this analysis.     

Stripping voltammetric determination of valsartan in bulk and pharmaceutical products

Stripping voltammetric determination of valsartan using a hanging mercury drop electrode (HMDE) was described. The method was based on adsorptive accumulation of the species at HMDE, followed by first harmonic alternating current AC stripping sweep at pH 6. The behavior of adsorptive stripping response was thoroughly studied under various experimental conditions, e.g. type of supporting electrolyte, pH, accumulation time, scan rate and mode of sweep. In Britton-Robinson buffer solution, a quasi-reversible reduction process involving transfer two electrons and two protons was took place. The response was linear over the concentration range of 0.08-0.64 microg/ml with regression coefficient 0.999 and limit of detection 0.02 microg/ml. The average of determinations of the cited compound in oral dosages with its standard deviation was 101.11 +/- 4.38%. The result obtained by the proposed method was compared with that obtained by the UV-spectrophotometric technique. Furthermore, the proposed method was successfully applied as stability-indicating method for determining valsartan in the presence of its acid induced degradation products.     

Differential-pulse adsorptive stripping voltammetric determination of the antibacterial lomefloxacin.

A differential-pulse adsorptive stripping voltammetric method for the determination of trace amounts of the antibacterial lomefloxacin is proposed. By using an accumulation potential of -0.30 V and a 2 min accumulation time, the linear concentration range of application was 1.0-10.0 ng ml(-1) of lomefloxacin, with a relative standard deviation of 3.8% (for a level of 5.0 ng ml(-1)) and a detection limit of 0.3 ng ml(-1). The method was applied to determination of lomefloxacin in human urine and serum samples. It was validated using HPLC as a reference method. Recovery levels of the method reached 100% in all cases.     

Polarographic behaviour of loratadine and its direct determination in pharmaceutical formulation and human plasma by cathodic adsorptive stripping voltammetry

The polarographic behaviour of the antihistaminic drug loratadine has been investigated in B.R. buffer solution of different pH values. Contradictory to that mentioned before in a previously published work, loratadine is electro-active at the mercury electrode. In B.R. buffer solution of pH values ≥6 it is reduced via a single 2-electrons irreversible wave corresponding to saturation of carbon–nitrogen double bond of the pyridine ring. The electrode reaction pathway was proposed and discussed. A sensitive differential pulse stripping voltammetric method based on controlled adsorptive accumulation of loratadine on a hanging mercury drop electrode has been developed for its direct determination at nanomolar concentrations without nitration of the drug. The optimized conditions for the direct cathodic adsorptive stripping voltammetric determination of the drug are: 0.1 M sodium hydroxide solution as a supporting electrolyte, accumulation potential, −1.2 V; accumulation time, 30 s; scan rate, 2–5 mV s⁻¹ and pulse amplitude 100 mV. The proposed procedure was applied for the assay of loratadine in pharmaceutical formulation and human plasma. The average recoveries were 99.32–99.44 and 100.33–102.99% with the RSD 0.27–0.42 and 0.39–0.90% in pharmaceutical formulation and human plasma, respectively. The limits of detection of 1.60×10⁻⁷ and 1.25×10⁻⁷ M loratadine were found in pharmaceutical formulation and human plasma, respectively.     

Stripping voltammetric determination of indapamide in serum at castor oil-based carbon paste electrodes

The diuretic drug indapamide has been characterized voltammetrically at carbon paste electrodes by means of cyclic and differential pulse voltammetry. An adsorptive stripping method at carbon paste electrode modified with castor oil for trace determination of indapamide was described. A study of the variation of the peak current with solution variables such as pH, ionic strength, concentration of indapamide, possible interference, and instrumental variables such as scan rate, pulse amplitude, preconcentration time, accumulation potential, paste composition has resulted in the optimization of the oxidation signal for analytical purposes. By anodic stripping differential pulse voltammetry, the calibration plot was linear in the range 5 x 10(-8) x 10(-7) M with a detection limit of 5 x 10(-9) M at carbon paste electrode modified with castor oil in pH 4.0. The preconcentration medium-exchange approach was utilized for selective determination of indapamide in spiked serum. A detection limit of 15 ng ml(-1) was obtained for dilute serum sample after 3 min accumulation and medium-exchange procedure.     

Adsorptive stripping voltammetric determination of cefetamet in human urine

On the basis of previously established mechanism of cefetamet (CEF) reduction, two methods were suggested for CEF determination-differential pulse polarographic and differential pulse adsorptive stripping voltammetric method. Two pH values were chosen, 2.0 and 8.4, where the electrochemical process was defined as one four-electron and two two-electron processes, respectively. The methods were performed in Britton-Robinson (BR) buffer and the corresponding calibration graphs were constructed and statistical parameters were evaluated. Applying the AdSV method at pH 2.0 linearity was achieved from 2 x 10(-8) to 2 x 10(-7) M with limit detection and limit determination of 4 x 10(-9) and 1.4 x 10(-8) M, respectively. At pH 8.4, the linearity was obtained between 6 x 10(-8) and 6 x 10(-7) M, with limit detection and limit determination of 1.5 x 10(-8) and 5 x 10(-8) M, respectively. Since the AdSV method enabled lower concentrations of CEF to be determined, this method was tested for CEF determination in spiked urine samples, and DPP method was used as a comparative one.     

Voltammetric assay of the anthelmintic veterinary drug nitroxynil in bulk form and formulation at a mercury electrode

The electrochemical behavior of the anthelmintic veterinary drug nitroxynil at the mercury electrode was studied in a series of Britton-Robinson universal buffer of pH 1.9-11 containing 20% (v/v) ethanol using dc-polarography cyclic voltammetry and controlled-potential coulometry. The voltammograms exhibited two irreversible cathodic steps over the pH range 1.9-10.2; the height of the first step is double that of the second one. Controlled-potential coulometry in the B-R universal buffer of pH 1.9-10 at a mercury pool working electrode revealed the consumption of four and two electrons via the first and second reduction steps, respectively, which attributed to reduction of the NO2 group to the hydroxylamine stage (first step), and then to the amine stage (second step). Three voltammetric analytical procedures including dc-polarography, differential-pulse adsorptive stripping voltammetry and square-wave adsorptive stripping voltammetry were optimized for the direct determination of bulk nitroxynil. The three proposed procedures were applied for analysis of bulk nitroxynil with limits of detection of 3 x 10(-5), 1.31 x 10(-8) and 8.4 x 10(-10)M and limits of quantification of 1 x 10(-5), 4.36 x 10(-8) and 2.80 x 10(-9)M, respectively. The three procedures were successfully applied to the determination of nitroxynil in formulation (Dovenix, 25% nitroxynil injection solution) without the necessity for sample pretreatment and/or time-consuming extraction steps prior to the analysis.     

Voltammetric studies on the antibiotic drug cefoperazone quantification and pharmacokinetic studies

A fully validated simple, sensitive and selective square-wave stripping voltammetry procedure was described for the trace quantification of cefoperazone in bulk form, formulations and human serum/plasma. The procedure was based on reduction of the adsorbed drug onto a hanging mercury drop electrode. The procedural conditions were optimized as: frequency=60Hz, scan increment=8mV, pulse amplitude=25mV, preconcentration potential=-0.3V (versus Ag/Ag/KCl(s)), preconcentration duration=60-150s and an acetate buffer of pH 4.2 as a supporting electrolyte. A limit of detection of 4.5x10(-10)M and a limit of quantitation of 1.5x10(-9)M bulk cefoperazone were achieved following preconcentration of the drug onto the hanging mercury drop electrode for 150s. The proposed square-wave adsorptive cathodic stripping voltammetric procedure was successfully applied for trace quantification of cefoperazone in human serum and plasma. The achieved limits of detection and quantitation of the drug in human serum were 6x10(-10)M (0.375ngml(-1)) and 2x10(-9)M (1.250ngml(-1)), respectively. The pharmacokinetic parameters of cefoperazone in plasma of hospitalized volunteers were successfully estimated.     

Stripping voltammetric and polarographic techniques for the determination of anti-fungal ketoconazole on the mercury electrode

The electroanalytical behaviour of ketoconazole in Britton-Robinson buffer is described. The reduction process on the hanging mercury drop electrode (HMDE) gives rise to one peak over -1.6 V (vs. Ag/AgCl/sat.KCl), within the pH range studied (4.7-9.6). The results showed that the reduction of ketoconazole is irreversible and the limiting current is adsorption controlled. The dependence of the peak current on the concentration was studied by means of different polarographic and voltammetric techniques. Using adsorptive stripping differential pulse voltammetry (AdS-DPV), the detection limit (DL) reached was 5.3 x 10(-11) mol l(-1). Two procedures, based on differential pulse polarography (DPP) and AdS-DPV in aqueous medium were developed for the determination of ketoconazole in a gel formulation and spiked urine samples, respectively.