A novel, simple and sensitive electrochemical method for the determination of ledipasvir (LED), the newly FDA approved Hepatitis C antiviral drug was developed and validated using ε-MnO2-modified graphite electrode. Two different MnO2 polymorphs (g- and ε-MnO2 nanoparticles) were synthesized and characterized using X-ray powder diffraction (XRD), Fourier transform infrared (FTIR), energy dispersive X-ray (EDX) and thermogravimetric analysis (TGA). Surface area measurements show that ε-MnO2 NPs have large surface area of 345 m2 /g, which is extremely high if compared to that of g-MnO2 NPs (38 m2 /g). In addition, a comprehensive study of the difference in the electrochemical behavior of LED while using pencil graphite electrode (PGE) modified with either g- or ε-MnO2 NPs is carried out. It was found that surface area and percentage of surface hydroxyls of MnO2 NPs are the key factors governing the sensitivity of the fabricated electrode toward the oxidation of the positively charged LED. Scanning electron microscopy (SEM) was employed to investigate the morphological shape of MnO2 NPs and the surface of the bare and modified electrodes. Moreover, cyclic voltammetry and electrochemical impedance spectroscopy (EIS) were used for the surface analysis of the modified electrodes. Based on the obtained results, ε-MnO2/PGE was applied as a selective and sensitive electrode for determination of LED. Under the optimized experimental conditions, ε-MnO2/PGE provides a linear response over the concentration range of 0.025e3.60 mmol L1 LED with a low limit of detection, which was found to be 5.10 nmol L1 (4.50 ng mL1 ) for the 1st peak and 9.20 nmol L1 (8.10 ng mL1 ) for the 2nd one. In addition, the oxidation behavior of LED is discussed with a full investigation of the oxidized product using FT-

A novel, simple and sensitive electrochemical method for the determination of ledipasvir (LED), the newly FDA approved Hepatitis C antiviral drug was developed and validated using ε-MnO2-modified graphite electrode. Two different MnO2 polymorphs (g- and ε-MnO2 nanoparticles) were synthesized and characterized using X-ray powder diffraction (XRD), Fourier transform infrared (FTIR), energy dispersive X-ray (EDX) and thermogravimetric analysis (TGA). Surface area measurements show that ε-MnO2 NPs have large surface area of 345 m2 /g, which is extremely high if compared to that of g-MnO2 NPs (38 m2 /g). In addition, a comprehensive study of the difference in the electrochemical behavior of LED while using pencil graphite electrode (PGE) modified with either g- or ε-MnO2 NPs is carried out. It was found that surface area and percentage of surface hydroxyls of MnO2 NPs are the key factors governing the sensitivity of the fabricated electrode toward the oxidation of the positively charged LED. Scanning electron microscopy (SEM) was employed to investigate the morphological shape of MnO2 NPs and the surface of the bare and modified electrodes. Moreover, cyclic voltammetry and electrochemical impedance spectroscopy (EIS) were used for the surface analysis of the modified electrodes. Based on the obtained results, ε-MnO2/PGE was applied as a selective and sensitive electrode for determination of LED. Under the optimized experimental conditions, ε-MnO2/PGE provides a linear response over the concentration range of 0.025e3.60 mmol L1 LED with a low limit of detection, which was found to be 5.10 nmol L1 (4.50 ng mL1 ) for the 1st peak and 9.20 nmol L1 (8.10 ng mL1 ) for the 2nd one. In addition, the oxidation behavior of LED is discussed with a full investigation of the oxidized product using FT-

Background: Atorvastatin (ATOR) is an antihyperlipoproteinemic drug, (3R, 5R)-7-[2-(4- fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-(propan-2-yl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid (Fig. 1a). It is used for the treatment of dyslipidemia and for prevention of different cardiovascular disorders. Methods: A simple and sensitive analytical procedure has been developed, optimized and validated by square wave voltammetry (SWV) using pencil graphite electrode (PGE) for the determination of atorvastatin calcium (ATOR) in both pharmaceutical formulation and biological samples. The voltammetric behavior of ATOR is studied using cyclic and square wave voltammetry in the presence of the ionic liquid-based surfactant, 1-tetradecyl-3-methylimidazolium bromide (C14MImBr). Results: The effect of different factors on the oxidation peak current of ATOR have been studied and optimized such as: pH, scan rate and the concentration of C14MImBr. Under optimized conditions in Britton–Robinson buffer (pH 3.3) containing 28 µmol L-1 C14MImBr, a linear response is obtained within the range of 1.34x10-6 to 10.8x10-6 mol L-1 ATOR, which is adequate for the quantitation of ATOR in real samples. The limit of detection was found to be 3.70x10-8 mol L-1. In addition, the developed method was applied to ATOR analysis in Lipitor tablets and spiked urine samples. Conclusion: This study represents the first report of electrochemical analysis of a pharmaceutical compound using ionic liquid-based surfactant. The analytical signal of ATOR is greatly enhanced in the presence of C14MImBr if compared to that obtained using a traditional cationic surfactant cetyltrimethylammonium bromide (CTAB).

Background: Atorvastatin (ATOR) is an antihyperlipoproteinemic drug, (3R, 5R)-7-[2-(4- fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-(propan-2-yl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid (Fig. 1a). It is used for the treatment of dyslipidemia and for prevention of different cardiovascular disorders. Methods: A simple and sensitive analytical procedure has been developed, optimized and validated by square wave voltammetry (SWV) using pencil graphite electrode (PGE) for the determination of atorvastatin calcium (ATOR) in both pharmaceutical formulation and biological samples. The voltammetric behavior of ATOR is studied using cyclic and square wave voltammetry in the presence of the ionic liquid-based surfactant, 1-tetradecyl-3-methylimidazolium bromide (C14MImBr). Results: The effect of different factors on the oxidation peak current of ATOR have been studied and optimized such as: pH, scan rate and the concentration of C14MImBr. Under optimized conditions in Britton–Robinson buffer (pH 3.3) containing 28 µmol L-1 C14MImBr, a linear response is obtained within the range of 1.34x10-6 to 10.8x10-6 mol L-1 ATOR, which is adequate for the quantitation of ATOR in real samples. The limit of detection was found to be 3.70x10-8 mol L-1. In addition, the developed method was applied to ATOR analysis in Lipitor tablets and spiked urine samples. Conclusion: This study represents the first report of electrochemical analysis of a pharmaceutical compound using ionic liquid-based surfactant. The analytical signal of ATOR is greatly enhanced in the presence of C14MImBr if compared to that obtained using a traditional cationic surfactant cetyltrimethylammonium bromide (CTAB).

Background: Atorvastatin (ATOR) is an antihyperlipoproteinemic drug, (3R, 5R)-7-[2-(4- fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-(propan-2-yl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid (Fig. 1a). It is used for the treatment of dyslipidemia and for prevention of different cardiovascular disorders. Methods: A simple and sensitive analytical procedure has been developed, optimized and validated by square wave voltammetry (SWV) using pencil graphite electrode (PGE) for the determination of atorvastatin calcium (ATOR) in both pharmaceutical formulation and biological samples. The voltammetric behavior of ATOR is studied using cyclic and square wave voltammetry in the presence of the ionic liquid-based surfactant, 1-tetradecyl-3-methylimidazolium bromide (C14MImBr). Results: The effect of different factors on the oxidation peak current of ATOR have been studied and optimized such as: pH, scan rate and the concentration of C14MImBr. Under optimized conditions in Britton–Robinson buffer (pH 3.3) containing 28 µmol L-1 C14MImBr, a linear response is obtained within the range of 1.34x10-6 to 10.8x10-6 mol L-1 ATOR, which is adequate for the quantitation of ATOR in real samples. The limit of detection was found to be 3.70x10-8 mol L-1. In addition, the developed method was applied to ATOR analysis in Lipitor tablets and spiked urine samples. Conclusion: This study represents the first report of electrochemical analysis of a pharmaceutical compound using ionic liquid-based surfactant. The analytical signal of ATOR is greatly enhanced in the presence of C14MImBr if compared to that obtained using a traditional cationic surfactant cetyltrimethylammonium bromide (CTAB).

The main aim of the current work is to investigate possible pharmacokinetic interactions between vardenafil hydrochloride (VAR), which is used for the treatment of erectile dysfunction and daclatasvir dihydrochloride (DAC), which is used for the treatment of chronic hepatitis C viral infection when they are concomitantly administered. Therefore, a sensitive and selective square-wave voltammetric method was developed and validated for simultaneous determination of VAR and DAC using disposable pencil graphite electrode (PGE) modified with xylenol orange (X.O.) flakes as an electrochemical sensor. A full investigation of the experimental parameters for obtaining the highest electroanalytical signal with sufficient resolution between the oxidation peaks of two compounds was performed. It was found that VAR and DAC were resolved on X.O./PGE with different potentials at 1.4 V and 0.9 V, respectively using Britton-Robinson buffer (pH 2.2) and 0.1 molL1 KCl as a supporting electrolyte. In addition, with the aid of cyclic voltammetry, a mechanistic scheme for the oxidation behaviour of both VAR and DAC was suggested. The proposed square wave voltammetric method was successfully applied for trace quantification of VAR and DAC in male rabbits. The suggested approach shows detection and quantification limits in rabbit plasma samples of 0.06 and 0.17 μmolL1, respectively for VAR and 0.13 and 0.39 μmolL1, respectively for DAC. The pharmacokinetic parameters of VAR alone and in combination with DAC after oral administration to rabbits were successfully estimated. The obtained results confirm that when DAC is co-administered with VAR, plasma concentration of VAR increases, which necessitates dose adjustment for VAR to prevent toxicological consequences in patients.

The main aim of the current work is to investigate possible pharmacokinetic interactions between vardenafil hydrochloride (VAR), which is used for the treatment of erectile dysfunction and daclatasvir dihydrochloride (DAC), which is used for the treatment of chronic hepatitis C viral infection when they are concomitantly administered. Therefore, a sensitive and selective square-wave voltammetric method was developed and validated for simultaneous determination of VAR and DAC using disposable pencil graphite electrode (PGE) modified with xylenol orange (X.O.) flakes as an electrochemical sensor. A full investigation of the experimental parameters for obtaining the highest electroanalytical signal with sufficient resolution between the oxidation peaks of two compounds was performed. It was found that VAR and DAC were resolved on X.O./PGE with different potentials at 1.4 V and 0.9 V, respectively using Britton-Robinson buffer (pH 2.2) and 0.1 molL1 KCl as a supporting electrolyte. In addition, with the aid of cyclic voltammetry, a mechanistic scheme for the oxidation behaviour of both VAR and DAC was suggested. The proposed square wave voltammetric method was successfully applied for trace quantification of VAR and DAC in male rabbits. The suggested approach shows detection and quantification limits in rabbit plasma samples of 0.06 and 0.17 μmolL1, respectively for VAR and 0.13 and 0.39 μmolL1, respectively for DAC. The pharmacokinetic parameters of VAR alone and in combination with DAC after oral administration to rabbits were successfully estimated. The obtained results confirm that when DAC is co-administered with VAR, plasma concentration of VAR increases, which necessitates dose adjustment for VAR to prevent toxicological consequences in patients.

The main aim of the current work is to investigate possible pharmacokinetic interactions between vardenafil hydrochloride (VAR), which is used for the treatment of erectile dysfunction and daclatasvir dihydrochloride (DAC), which is used for the treatment of chronic hepatitis C viral infection when they are concomitantly administered. Therefore, a sensitive and selective square-wave voltammetric method was developed and validated for simultaneous determination of VAR and DAC using disposable pencil graphite electrode (PGE) modified with xylenol orange (X.O.) flakes as an electrochemical sensor. A full investigation of the experimental parameters for obtaining the highest electroanalytical signal with sufficient resolution between the oxidation peaks of two compounds was performed. It was found that VAR and DAC were resolved on X.O./PGE with different potentials at 1.4 V and 0.9 V, respectively using Britton-Robinson buffer (pH 2.2) and 0.1 molL1 KCl as a supporting electrolyte. In addition, with the aid of cyclic voltammetry, a mechanistic scheme for the oxidation behaviour of both VAR and DAC was suggested. The proposed square wave voltammetric method was successfully applied for trace quantification of VAR and DAC in male rabbits. The suggested approach shows detection and quantification limits in rabbit plasma samples of 0.06 and 0.17 μmolL1, respectively for VAR and 0.13 and 0.39 μmolL1, respectively for DAC. The pharmacokinetic parameters of VAR alone and in combination with DAC after oral administration to rabbits were successfully estimated. The obtained results confirm that when DAC is co-administered with VAR, plasma concentration of VAR increases, which necessitates dose adjustment for VAR to prevent toxicological consequences in patients.

The main aim of the current work is to investigate possible pharmacokinetic interactions between vardenafil hydrochloride (VAR), which is used for the treatment of erectile dysfunction and daclatasvir dihydrochloride (DAC), which is used for the treatment of chronic hepatitis C viral infection when they are concomitantly administered. Therefore, a sensitive and selective square-wave voltammetric method was developed and validated for simultaneous determination of VAR and DAC using disposable pencil graphite electrode (PGE) modified with xylenol orange (X.O.) flakes as an electrochemical sensor. A full investigation of the experimental parameters for obtaining the highest electroanalytical signal with sufficient resolution between the oxidation peaks of two compounds was performed. It was found that VAR and DAC were resolved on X.O./PGE with different potentials at 1.4 V and 0.9 V, respectively using Britton-Robinson buffer (pH 2.2) and 0.1 molL1 KCl as a supporting electrolyte. In addition, with the aid of cyclic voltammetry, a mechanistic scheme for the oxidation behaviour of both VAR and DAC was suggested. The proposed square wave voltammetric method was successfully applied for trace quantification of VAR and DAC in male rabbits. The suggested approach shows detection and quantification limits in rabbit plasma samples of 0.06 and 0.17 μmolL1, respectively for VAR and 0.13 and 0.39 μmolL1, respectively for DAC. The pharmacokinetic parameters of VAR alone and in combination with DAC after oral administration to rabbits were successfully estimated. The obtained results confirm that when DAC is co-administered with VAR, plasma concentration of VAR increases, which necessitates dose adjustment for VAR to prevent toxicological consequences in patients.

Two new, simple, selective, and highly sensitive spectrofluorimetric methods were developed and validated for the determination of the antiepileptic drug; retigabine (RTG). The first method (Method-I) depends on enhancement of the weak native fluorescence of RTG via the use of an organized medium; sodium dodecyl sulphate (SDS) in acetate buffer (pH 3.74). The second method (Method-II) depends on the enhancement of RTG weak native fluorescence through complexation with a macromolecule; beta cyclodextrin (β-CD) in phosphate buffer (pH 3.20). A full study of different experimental parameters influencing the fluorescence intensity was carried out. In addition, a thorough investigation of the fluorescence quantum yield, fluorophore brightness and mechanism of fluorescence enhancement was performed. A seven-fold improvement in the fluorescence intensity was brought by the first method, whereas a six and half-fold enhancement of the fluorescence intensity was obtained by the second one. Linearity was achieved over wide ranges (0.05–12.5 μg mL−1) and (0.05–15 μg mL−1) with low limits of detection (LOD) of 10.6 and 14.3 ng mL−1, and limits of quantification (LOQ) of 32.0 and 43.2 ng mL−1 for (Method-I) and (Method-II), respectively. The proposed methods were validated according to ICH and US-FDA guidelines. The applicability of the proposed methods was tested for determination of RTG in its pharmaceutical dosage forms, and to study the stability of RTG under different stress conditions according to ICH guidelines including alkaline, acidic, oxidative, thermal, and photolytic stress conditions. Moreover, the high sensitivity achieved by the proposed methods permitted the determination and detection of RTG in both spiked and real rabbit plasma samples utilizing a simple protein precipitation step followed by liquid-liquid extraction method. Percentage recoveries from rabbit plasma samples were within the acceptable limits; (93.47–104.74%) and (91.33–105.70%) for (Method-I) and (Method-II), respectively.