Nasr M. El-Abasawi

Experimental design of membrane sensor for selective determination of phenazopyridine hydrochloride based on computational calculations.

Computational study has been done electronically and geometrically to select the most suitable ionophore to design a novel sensitive and selective electrochemical sensor for phenazopyridine hydrochloride (PAP). This study has revealed that sodium tetraphenylbarate (NaTPB) fits better with PAP than potassium tetrakis (KTClPB). The sensor design is based on the ion pair of PAP with NaTPB using dioctyl phthalate as a plasticizer. Under optimum conditions, the proposed sensor shows the slope of 59.5 mV per concentration decade in the concentration range of 1.0 × 10(-2)-1.0 × 10(-5) M with detection limit 8.5 × 10(-6) M. The sensor exhibits a very good selectivity for PAP with respect to a large number of interfering species as inorganic cations and sugars. The sensor enables track of determining PAP in the presence of its oxidative degradation product 2, 3, 6-Triaminopyridine, which is also its toxic metabolite. The proposed sensor has been successfully applied for the selective determination of PAP in pharmaceutical formulation. Also, the obtained results have been statistically compared to a reported electrochemical method indicating no significant difference between the investigated method and the reported one with respect to accuracy and precision.

Different spectrophotometric methods applied for the analysis of simeprevir in the presence of its oxidative degradation product: Acomparative study

Five simple spectrophotometric methods were developed for the determination of simeprevir in the presence of its oxidative degradation product namely, ratio difference, mean centering, derivative ratio using the Savitsky-Golay filters, second derivative and continuous wavelet transform. These methods are linear in the range of 2.5-40μg/mL and validated according to the ICH guidelines. The obtained results of accuracy, repeatability and precision were found to be within the acceptable limits. The specificity of the proposed methods was tested using laboratory prepared mixtures and assessed by applying the standard addition technique. Furthermore, these methods were statistically comparable to RP-HPLC method and good results were obtained. So, they can be used for the routine analysis of simeprevir in quality-control laboratories.

Application of different spectrophotometric methods for simultaneous determination of elbasvir and grazoprevir in pharmaceutical preparation

The first three UV spectrophotometric methods have been developed of simultaneous determination of two new FDA approved drugs namely; elbasvir and grazoprevir in their combined pharmaceutical dosage form. These methods include simultaneous equation, partial least squares with and without variable selection procedure (genetic algorithm). For simultaneous equation method, the absorbance values at 369 (λmax of elbasvir) and 253nm (λmax of grazoprevir) have been selected for the formation of two simultaneous equations required for the mathematical processing and quantitative analysis of the studied drugs. Alternatively, the partial least squares with and without variable selection procedure (genetic algorithm) have been applied in the spectra analysis because the synchronous inclusion of many unreal wavelengths rather than by using a single or dual wavelength which greatly increases the precision and predictive ability of the methods. Successfully assay of the drugs in their pharmaceutical formulation has been done by the proposed methods. Statistically comparative analysis for the obtained results with the manufacturing methods has been performed. It is noteworthy to mention that there was no significant difference between the proposed methods and the manufacturing one with respect to the validation parameters.

Stability-indicating HPLC-DAD Method for the Determination of Simeprevir

Abstract Simeprevir is a novel direct acting antiviral agent against hepatitis C virus. In the present work, a rapid, specific and reproducible reversed phase high performance liquid chromatography with diode array detection (HPLC-DAD) method has been developed and validated for the determination of simeprevir in the presence of its forced degradation products. The drug was subjected to variable stress conditions including hydrolysis, oxidation, thermal and photolysis. The drug was found to be labile to acidic hydrolysis, basic hydrolysis, oxidation and photolysis but stable in thermal and neutral hydrolytic conditions. Successful chromatographic separation of simeprevir was achieved on Discovery® HS C18 column at a flow rate of 1 mL/ min using mobile phase of acetonitrile. The eluents were monitored by the diode array detector and peak area values were measured at 288 nm. The validity of the method was assessed by evaluating accuracy, precision, specificity and robustness. The linear regression analysis data for the calibration curve shows a good relationship in the range of 1.5 - 45 μg/mL. The developed method was successfully applied for the estimation of simeprevir in its commercial dosage form and could be used for the routine analysis of the studied drug in quality control laboratories.

Colorimetric estimation of alfuzosin hydrochloride in pharmaceutical preparation based on computational studies

Computational and theoretical studies were done electronically and geometrically to find a suitable, selective and sensitive coupling agent applicable for diazocoupling estimation of alfuzosin hydrochloride (ALF). These studies revealed that 8-hydroxyquinoline (8-HQ) fits better with ALF than other coupling agents based on its higher calculated interaction energy. The proposed method is based on the formation of a red colored chromogen through the reaction of ALF with sodium nitrite in acid medium to form a diazonium ion, which was coupled with 8-HQ. Different variables affecting the reactions are optimized. Beers law is obeyed over the concentration range of 1–12 μg ml−1. The Jobs plot analysis was applied and the stoichiometric ratio of ALF : 8-HQ was found to be 1 : 1. The method was successfully applied to the determination of ALF in pharmaceutical formulations with good accuracy and precision.

Comparative Study of Different Spectrophotometric Methods for Determination of Phenazopyridine Hydrochloride in the Presence of its Oxidative Degradation Product

Abstract Four stability indicating spectrophotometric methods have been developed for selective determination of phenazopyridine hydrochloride (PAP) in the presence of its oxidative degradation product 2,3,6-triaminopyridine (TAP). The described spectrophotometric methods namely; first derivative (1D), ratio difference spectrophotometric method (RDSM), first derivative of ratio spectra (1DD, and dual wavelength (DW). For 1D method, the peak amplitudes at 370 nm were measure, while the difference between 428 and 276 nm in peak amplitudes were measured for RDSM. On the other hand, the peak amplitudes at 360 nm were measured for 1DD, while the difference in the absorbance between 425 and 256 nm were measured for DW. The regression analysis data for the calibration plots of PAP showed a good linear relationship over the concentration range of 1-14 μg/ml by the four proposed methods. The proposed methods have been successfully applied to the assay of PAP in pharmaceutical formulation. Also, the obtained results have been statistically compared to a reported HPLC method to give a conclusion that there is no significant difference between the investigated methods and the reported one with respect to validation parameters.

Simultaneous Spectrophotometric Determination of Elbasvir and Grazoprevir in a Pharmaceutical Preparation

Three UV spectrophotometric methods have been developed for the simultaneous determination of two new Food and Drug Administration-approved drugs, elbasvir (EBV) and grazoprevir (GRV), in their combined pharmaceutical dosage form. These methods include dual wavelength (DW), classic least-squares (CLS), and principal component regression (PCR). To achieve the DW method, two wavelengths were chosen for each drug in a way to ensure the difference in absorbance was zero from one drug to the other. GRV revealed equal absorbance at 351 and 315 nm, for which the distinctions in absorbance were measured for the determination of EBV. In the same way, distinctions in absorbance at 375 and 334.5 nm were measured for the determination of GRV. Alternatively, the CLS and PCR models were applied to the spectra analysis because the synchronous inclusion of many unreal wavelengths rather than using a single wavelength greatly increased the precision and predictive ability of the methods. The proposed methods were successfully applied to the assay of these drugs in their pharmaceutical formulation. The obtained results were statistically compared with manufacturing methods. The results conclude that there was no significant difference between the proposed methods and the manufacturing method with respect to accuracy and precision.

Different Spectrophotometric Methods Manipulating Ratio Spectra Applied for the Analysis of Aclidinium in Duaklir® Genuair® Inhalation Powder

Two simple, accurate, and selective spectrophotometric methods were developed to determine aclidinium in the presence of formoterol as interferent compound in Duaklir Genuair inhalation powder. The methods under study are ratio derivative and ratio subtraction spectrophotometric methods. These methods are based on different mathematical processing of the obtained ratio spectra. The methods are linear over the concentration range of 5–50 µg/mL for aclidinium and validated according to the ICH guidelines. The accuracy and precision are found to be within the acceptable limits and assessed by applying the standard addition technique. The specificity of the proposed methods was tested using laboratory-prepared mixtures. Furthermore, the methods were statistically compared to the reported RP-HPLC method, and good results were obtained.

Simultaneous determination of rosuvastatin and propranolol in their binary mixture by synchronous spectrofluorimetry

Simultaneous determination of rosuvastatin calcium and propranolol hydrochloride using the first derivative synchronous spectrofluorimetry was described. This method involves measuring the synchronous fluorescence of both drugs in ethanol using, ∆ λ = 60 nm then the first derivative was recorded and the peak amplitudes were measured at 350 and 374 nm for rosuvastatin calcium and propranolol hydrochloride, respectively. Under the optimum conditions, the linear ranges of rosuvastatin calcium and propranolol hydrochloride were 0.2-2 μg/mL and 0.1-1 μg/mL, respectively. The method was used for quantitative analysis of the drugs in raw materials and pharmaceutical dosage form. The validity of the proposed method was assessed according to an international conference on harmonization (ICH) guidelines.

Application of different analytical techniques for determination of velpatsvir and sofosbuvir in the pharmaceutical preparation

Abstract Three analytical methods have been developed and applied for determination of velapatasvir and sofosbuvir in their new FDA-approved pharmaceutical dosage form. Capillary electrophoresis has been introduced as a powerful separation analytical technique for the simultaneous analysis of the studied drugs within a shorter analytical run time. Separation has been carried out on fused silica capillary (50 cm × 75 µm internal diameter), background electrolyte solution consisted of borate buffer (40 mM, pH 10) and UV detection carried out at 225 nm. Also, two mathematical spectrophotometric methods have been applied for resolving the recorded overlapping UV spectra of velpatasvir and sofosbuvir. Direct zero-order spectrophotometric determination of velpatasvir was done at 339 nm where no significance absorbance or contribution from sofosbuvir was observed. Savitsky–Golay filters signal processing has been achieved to enable determination of sofosbuvir in its binary mixture with velpatasvir. The amplitude of the first derivative of the sofosbuvir spectra, calculated by Savitsky–Golay filters, at 251 nm enabled the determination of sofosbuvir without any contribution of velpatasvir. The described methods have been validated and applied for determination of the studied drugs in their pharmaceutical dosage form. Graphical Abstract