Simultaneous Determination of Amlodipine and Irbesartan in their Pharmaceutical Formulations by Square-Wave Voltammetry.

BACKGROUND: Hypertension is one of the most important health problems in the world and irbesartan and amlodipine are used in combination in various dosages for the treatment of high blood pressure. OBJECTIVE: The aim of this study is to develop a fast, easy, sensitive, accurate, and precise squarewave voltammetry method for simultaneous determination of irbesartan and amlodipine besylate from pharmaceutical formulations at a hanging mercury drop electrode. METHODS: In the applied method, since both active substances gave a peak at different potentials, no interference occurred between them. In optimization studies, Britton-Robinson buffer of pH 8.0 was chosen, in which the most appropriate peak shape and maximum peak current were observed. At the same time, as a result of instrumental parameter optimization to obtain reproducible results, 6 mV for scan increment, 30 mV for pulse amplitude, and 50 Hz for frequency were found suitable. RESULTS: As a result of the calibration studies of the optimized method, linear working ranges were determined as 1.00-13.08 µg mL-1 for irbesartan and 5.83-16.51 µg mL-1 for amlodipine besylate. Limit of detection and limit of quantitation values were respectively calculated as 0.63 and 1.00 µg mL-1 for irbesartan and 0.50 and 1.98 µg mL-1 for amlodipine besylate. The results of precision values (RSD) ranged from 0.67% to 2.31% for irbesartan and 0.65% to 1.49% for amlodipine besylate. Accuracy values were calculated as -0.15% to 1.63% for irbesartan and -0.07% to 3.78% for amlodipine besylate. The results obtained from the recovery studies ranged from 101.05% to 102.78% and from 98.88% to 102.20% for amlodipine besylate and irbesartan, respectively. CONCLUSION: After the validation studies of the developed method were carried out, it was successfully applied to pharmaceutical formulations containing these active substances.

Electrochemical Behavior and Square-Wave Stripping Voltammetric Determination of Roflumilast in Pharmaceutical Dosage Forms.

BACKGROUND: Bronchial asthma and chronic obstructive pulmonary disease (COPD) are among the most common chronic diseases. Roflumilast is a novel, potent, selective, and long-acting phosphodiesterase 4 (PDE-4) inhibitor for the treatment of bronchial asthma and COPD. It has anti-inflammatory effects, and it has been shown to reduce exacerbations and improve pulmonary function in patients with COPD. Although there have been some other analytical methodologies reported for the determination of roflumilast in pharmaceutical dosage forms, there has not yet been any electrochemical methodology proposed for determination of this unique active pharmaceutical ingredient in its dosage forms. OBJECTIVE: The aim of this study was to develop an easily applied, selective, sensitive, accurate, and precise square-wave stripping voltammetric (SWSV) method for the determination of roflumilast in its pharmaceutical dosage forms. In addition, the electrochemical behavior of roflumilast was investigated. METHODS: The proposed method was based on electrochemical reduction of roflumilast at a hanging mercury drop electrode (HMDE) in 0.1 M K2HPO4 and 0.1 M Na2B4O7 (1:1, v/v) buffer at pH 5.0. Two reduction peaks were observed at -1150 mV and -1260 mV with 30 s of accumulation time and -850 mV of accumulation potential time versus Ag/AgCl reference electrode. RESULTS: The highest peak current values with the best peak definition were observed at a frequency of 50 Hz, scan increment of 5 mV, and pulse amplitude 25 mV. The proposed method was validated by evaluating validation parameters such as linearity, sensitivity, repeatability, accuracy, precision, selectivity, recovery, robustness, and ruggedness. A good linear correlation (r=0.9948) was obtained between the electrochemical response of roflumilast and its concentration in the range of 0.74-3.05 µg mL-1 under the optimum conditions. The obtained accuracy results were between 2.04% and -2.04% while the relative standard deviation of the results was at least 2.78% for intraday and inter-day studies. The mean recovery for the real applications was 100.63% ± 0.52. The electrochemical behavior of roflumilast was investigated by cyclic voltammetry. The cyclic voltammogram of roflumilast exhibited two peaks and the reduction reaction was reversible. CONCLUSION: This developed and validated SWSV method was applied successfully for the determination of roflumilast in tablet dosage form (Daxas®) to assess active roflumilast content. Since high- -performance liquid chromatography is a dominant technique in industry for quality control of active pharmaceutical ingredients, the finding in the present study demonstrated that square-wave stripping voltammetry could be easily utilized in routine applications to determine roflumilast content in its dosage forms.

Lower plasma pantoprazole level predicts Helicobacter pylori treatment failure in patients with type 2 diabetes mellitus.

OBJECTIVE: We aimed to compare the plasma pantoprazole level (PPL) between patients with type 2 diabetes mellitus and non-diabetic patients during Helicobacter pylori (H. pylori) eradication treatment and to explore the role of PPL in predicting the treatment success rates. METHODS: This study included 40 diabetic and 40 non-diabetic treatment-naive H. pylori-infected patients. Bismuth-based standard quadruple treatment for H. pylori eradication was used for 14 days in both groups. PPL was measured using the square-wave voltammetry method. RESULTS: H. pylori eradication rate (60.0% vs 87.5%, P = 0.005) and PPL (0.25 ± 0.03 µg/mL vs 0.34 ± 0.03 µg/mL, P < 0.001) was significantly lower in the diabetic group compared with the controls. Patients with treatment failure had lower PPL than those with successful treatment (P < 0.001). The receiver operating characteristics curve demonstrated that PPL had a significant predictive value for the outcome of H. pylori eradication. CONCLUSION: Type 2 diabetic patients had lower PPL than the non-diabetic controls, which led to their lower H. pylori eradication rates.

Voltammetric determination of candesartan cilexetil in its Cu(II) complex and application to pharmaceutical formulations.

The aim of this study was to develop a new, simple, rapid, and sensitive square-wave adsorptive stripping voltammetric method for the determination of candesartan cilexetil in bulk form and pharmaceutical formulations by complex formation with Cu(II). The experimental and instrumental parameters affecting the response of the candesartan cilexetil-Cu(II) complex were investigated and optimized. This method was based on electrochemical reduction of candesartan cilexetil-Cu(II) complex at a hanging mercury drop electrode in phosphate buffer at pH 3.0 containing CuCl2 x 2H2O. A well-defined reduction peak was observed at -325 mV with 30 s accumulation time and -150 mV accumulation potential versus an Ag/AgCl reference electrode in the proposed method. The developed voltammetric method was validated in terms of linearity, sensitivity, precision, accuracy, recovery, selectivity, robustness, and ruggedness. The linear calibration range was 0.50-1.77 microg/mL (r = 0.9972). The LOD and LOQ of this method were 0.10 and 0.50 microg/mL (n = 7), respectively. The developed method was fully validated and applied to the pharmaceutical formulations, including candesartan cilexetil.

Optimisation, validation and application of a capillary electrophoretic method for the determination of zafirlukast in pharmaceutical formulations.

Zafirlukast is a selective and competitive orally administered inhibitor of the cysteinyl leukotrienes and currently indicated for the prophylaxis and treatment chronic asthma. A simple, rapid, reliable capillary zone electrophoresis method for the determination of ZAF in pharmaceutical formulations was developed and validated. The influence of buffer concentration, buffer pH, organic modifier, capillary temperature, applied voltage and injection time was systemically investigated in a fused silica capillary (i.d. 50 microm, total length 80.5 cm and effective length 72.0 cm). Optimum results were obtained with 50mM borate buffer at pH 8.50, capillary temperature 25 degrees C and applied voltage 30 kV. The samples were injected hydrodynamically for 3s at 50 mbar. Detection wavelength was set at 240 nm. Meloxicam was used as internal standard. The method was suitably validated with respect to linearity, limit of detection and quantification, accuracy, precision, selectivity, robustness and ruggedness. The linear calibration range was 2.00-80.00 microg mL(-1) and the limits of detection and quantification were 0.75 and 2.00 microg mL(-1) with R.S.D. of 3.88 and 2.75%, respectively. The proposed method was applied for the determination of ZAF in its pharmaceutical formulations. The results obtained from developed method were compared with a HPLC method reported in the literature and no significant difference was found statistically.

A reversed-phase high-performance liquid chromatographic method for the determination of zafirlukast in pharmaceutical formulations and human plasma.

Zafirlukast (ZAF) is a leukotriene receptor antagonist used in the treatment of chronic asthma. In this study, a simple and sensitive reversed-phase, high-performance liquid chromatographic method was developed for the determination of ZAF in pharmaceutical formulations and human plasma. Piribedil was used as an internal standard. Analysis was carried out on a Nucleosil C18 100 A (150 mm x 4.6 mm id, 5 Vm) column with acetonitrile-pH 3.0 acetate buffer (70 + 30, v/v) as the mobile phase at a flow rate of 0.8 mL/min. The peak was detected by an ultraviolet detector set at a wavelength of 240 nm. The retention times were about 3.9 min for piribedil and 5.8 min for ZAF. The developed method was applied to the determination of ZAF in its pharmaceutical formulation and spiked human plasma. For quantification of ZAF in spiked plasma, proteins were precipitated with ethanol before chromatographic analysis. The calibration range was linear from 49.69-437.50 ng/mL in spiked plasma. The absolute recovery from spiked plasma was 98.73 +/- 0.42% at a concentration of 254.78 ng/mL of ZAF. No endogenous substances from plasma were found to interfere.

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.

Determination of piribedil in pharmaceutical formulations by micellar electrokinetic capillary chromatography.

A fast and simple micellar electrokinetic capillary chromatographic method was developed for the analysis of piribedil in pharmaceutical formulations. The effects of buffer concentration, buffer pH, sodium dodecyl sulphate (SDS) concentration, organic modifier, applied voltage and injection time were investigated. Optimum results were obtained with a 50 mM borate buffer at pH 8.0 containing 50 mM SDS by using a fused silica capillary (50 microm internal diameter, 72 cm effective length). The sample was injected hydrodynamically for 4 s at 50 mbar pressure and the applied voltage was +30 kV. The detection wavelength was set at 205 nm. Diflunisal was used as an internal standard. The analysis was performed at 25 degrees C and the total run time was 14 min. The method was suitably validated with respect to linearity range, limit of detection and quantification, precision, accuracy, specificity and robustness. The linear calibration range was 5-100 microg mL(-1) and the limit of detection was determined as 1 microg mL(-1). The method developed was successfully applied to the determination of piribedil in pharmaceutical formulations. The results were compared with a spectrophotometric method reported in the literature and no significant difference was found statistically.

Determination of nifedipine in human plasma by square wave adsorptive stripping voltammetry.

A simple, sensitive and selective square-wave adsorptive stripping voltammetric method has been developed and validated for the determination of nifedipine (NIF) in plasma. The assay was performed after single extraction of NIF from alkalinised plasma into organic phase. The adsorption behaviour of NIF on a hanging mercury drop electrode (HMDE) was explored by square-wave and cyclic voltammetry. The drug was accumulated at HMDE and a well-defined peak was obtained at -730 mV versus Ag/AgCl in borate buffer of pH 9.0 including 0.01 M KCl. The linear concentration range was 2.89 x 10(-9) M-3.61 x 10(-7) M (1.00-125.01 ng ml(-1)) when using 30 s accumulation time at -300 mV. Limit of detection and limit of quantification were 1.21 x 10(-9) M (0.42 ng ml(-1)) and 2.89 x 10(-9) M (1.00 ng ml(-1)) respectively. The intra-day relative standard deviation (RSD) ranged from 1.93 to 4.12% at three concentrations and the inter-day RSDs varied from 2.53 to 6.68%. The method was applied, to the plasma of pregnant women suffering from pregnancy induced hypertension, for the determination of NIF. The percentage recoveries varied from 96.26 to 99.49%. It has been shown that NIF could be determined in the presence of its main metabolite (dehydronifedipine) by the developed method.

Two derivative spectrophotometric determinations of indapamide in pharmaceutical dosage forms.

Simple, fast and reliable derivative spectrophotometric methods were developed for determination of indapamide in bulk and pharmaceutical dosage forms. The solutions of standard and the sample were prepared in methanol. The quantitative determination of the drug was carried out using the first-derivative values measured at 252.8 nm (N=6) and the second-derivative values measured at 260.4 nm (N=9). Calibration graphs constructed at their wavelengths of determination were linear in the concentration range of indapamide using peak to zero 1.00-30.00 microg ml(-1) for first-derivative and 1.00-35.00 microg ml(-1) for second-derivative spectrophotometric method. The developed methods were successfully applied for the assay of pharmaceutical dosage forms which do not require any preliminary separation or treatment of the samples. The details of the statistical treatment of analytical data are also presented. The results obtained from two derivative spectrophotometry were compared with a spectrophotometric method reported in literature and no significant difference was found statistically.

Spectrophotometric determination of enoxacin as ion-pairs with bromophenol blue and bromocresol purple in bulk and pharmaceutical dosage form.

Three simple, accurate and sensitive spectrophotometric methods were developed for determination of enoxacin. The methods based on extraction of this drug into chloroform as ion pairs with sulphonphthalein dyes as bromophenol blue and bromocresol purple. The optimum conditions of the reactions were studied and optimized. The absorbance of yellow products was measured at 412 nm for enoxacin-bromophenol blue and 410 nm for enoxacin-bromocresol purple. Linearity ranges were found to be 2.0-20.0 microg ml(-1) for enoxacin-bromophenol blue and 0.77-17.62 microg ml(-1) for enoxacin-bromocresol purple. The detection limits were found to be 0.084 microg ml(-1) and 0.193 microg ml(-1) for enoxacin-bromophenol blue and enoxacin-bromocresol purple, respectively. The composition of the ion pairs was found 1:1 by Job's method. The developed methods were applied successfully for the determination of this drug in pharmaceutical preparation. The data obtained by developed methods were compared with the spectrophotometric method in literature. No differences were found statistically.