Ahmed H. Abdelazim

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.

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.

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.

Second derivative spectrophotometric and synchronous spectrofluorometric determination of lesinurad in the presence of its oxidative degradation product

Lesinurad is a novel selective uric acid reabsorption inhibitor which has been recently approved for the treatment of chronic gout. The present study is considered to report the first analytical methods for the quantitative and selective determination of lesinurad in the presence of its oxidative degradation product. Complete oxidative degradation of lesinurad has been done after extensive trials under different conditions. Identification of the lesinurad oxidative degradation product has been checked via mass spectrometry. Derivative mathematical manipulation has been introduced to resolve the overlap that existed between the recorded UV absorption spectra or the synchronous fluorescence spectra of lesinurad and its degradation product. The second derivative of the UV spectra has enabled the estimation of lesinurad by measuring the peak amplitudes at 279 nm without any interference from its degradation product. Alternatively, the second derivative of the synchronous fluorescence spectra has enabled the selective determination of lesinurad by measuring the peak amplitudes at 370 nm (Δλ = 60) nm without any interference from the degradation product. The developed methods have been optimized, validated and applied for quantitative determination of the studied drug in its pharmaceutical dosage form.

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

Validated Stability Indicating High Performance Liquid Chromatographic Determination of Lesinurad

Lesinurad is a novel selective uric acid reabsorption inhibitor which has been newly approved for the treatment of the chronic gout. The behavior of lesinurad under various stress conditions (hydrolysis, oxidation, thermal and photolysis) has been investigated as per ICH guidelines. The drug has been found to be labile to acidic hydrolysis, basic hydrolysis and oxidation but stable in neutral, thermal and photolytic conditions. A high performance liquid chromatographic method has been developed for selective determination of the studied drug in the presence of its related degradation products. Good chromatographic resolution has been achieved using a reversed phase BDS Hypersil C18 stationary phase with an isocratic elution of a mobile phase consists of acetonitrile:water (65:35, v/v) at a flow rate of 1 mL/min and UV detection at 290 nm. Two degradation products have been identified by IR and mass spectral scans. The method was validated according to ICH guidelines. The linearity range has been found to be acceptable over the concentration range of 1-20 μg/mL. The developed method has been successfully applied for the estimation of lesinurad in its pharmaceutical dosage form and could be used for the routine analysis of the studied drug in the quality control laboratories.

Simultaneous Determination of Elbasvir and Grazoprevir in Their Pharmaceutical Preparation Using High-Performance Liquid Chromatographic Method

A high-performance liquid chromatographic method has been developed for simultaneous determination of elbasvir and grazoprevir; two new Food and Drug Administration (FDA) approved drugs. The two drugs were co-formulated for treatment of hepatitis C virus in their combined pharmaceutical dosage form. The chromatographic separation has been achieved using a reversed phase BDS Hypersil C18 column with a mobile phase consists of acetonitrile:methanol (50:50, v/v) at flow rate of 1 mL/min and UV detection at 253 nm. Computational investigation for finding the best stationary phase revealed that C18 column fits better for the simultaneous chromatographic analysis of the studied drugs. Linearity, accuracy and precision have been found to be acceptable over the concentration range of 1-20 μg/mL for the studied drugs. The described method has been successfully applied for simultaneous determination of the studied drugs in their pharmaceutical dosage form.

Application of an HPLC Method for Selective Determination of Phenazopyridine Hydrochloride: Theoretical and Practical Investigations

HPLC method was developed for the selective determination of phenazopyridine hydrochloride (PAP) in the presence of its computationally selected metabolite. Density functional theory was applied as a computational model to study the energy of PAP metabolites, and the results revealed that 2,3,6-triaminopyridine (TAP) is the most stable metabolite. Good resolution and separation of PAP from TAP was achieved using a reversed-phase BDS Hypersil C18 column with a mobile phase consisting of acetonitrile-water (75 + 25, v/v) at flow rate of 1 mL/min and with UV detection at 280 nm. The linear regression analysis data for the calibration plot of PAP showed a good linear relationship over the concentration range of 5-45 μg/mL, with an LOD of 0.773 μg/mL. Moreover, a theoretical investigation of the relationship between the stationary phase and the studied molecules was performed to confirm the experimental results. The proposed method was successfully applied for the selective determination of PAP in pharmaceutical formulation. In addition, the obtained results were statistically compared to a reported method, with no significant differences found between the investigated method and the reported one with respect to accuracy and precision.