Azza H. Rageh

Analysis of cephalosporin antibiotics

A comprehensive review with 276 references for the analysis of members of an important class of drugs, cephalosporin antibiotics, is presented. The review covers most of the methods described for the analysis of these drugs in pure forms, in different pharmaceutical dosage forms and in biological fluids.

Kinetic spectrophotometric determination of certain cephalosporins using oxidized quercetin reagent.

A simple, precise and accurate kinetic spectrophotometric method for determination of cefoperazone sodium, cefazolin sodium and ceftriaxone sodium in bulk and in pharmaceutical formulations has been developed. The method is based upon a kinetic investigation of the reaction of the drug with oxidized quercetin reagent at room temperature for a fixed time of 30 min. The decrease in absorbance after the addition of the drug was measured at 510 nm. The absorbance concentration plot was rectilinear over the range 80-400 microg mL(-1) for all studied drugs. The concentration of the studied drugs was calculated using the corresponding calibration equation for the fixed time method. The determination of the studied drugs by initial rate, variable time and rate-constant methods was feasible with the calibration equations obtained but the fixed time method has been found to be more applicable. The analytical performance of the method, in terms of accuracy and precision, was statistically validated; the results were satisfactory. The method has been successfully applied to the determination of the studied drugs in commercial pharmaceutical formulations. Statistical comparison of the results with a well established reported method showed excellent agreement and proved that there is no significant difference in the accuracy and precision.

Lipophilicity estimation of statins as a decisive physicochemical parameter for their hepato-selectivity using reversed-phase thin layer chromatography

HighlightsRP‐TLC behavior of statins was studied using binary mobile phases.Determination of retention paramters (RM0 or C0) of six members of statins.Experimentally‐determined lipophilicity values were correlated with those reported in databases.RM0 or C0 were applied for prediction of physicochemical properties and pharmacokinetics of statins.QSRR and QSPR models using RM0 or C0 values are considered as good predictors for extra‐hepatic distributions of statins. Abstract Lipophilicity plays a crucial role in determining the hepato‐selectivity and hence, the biological activity and the associated side effects of statins. Herein, the employment of RP‐TLC for estimation of lipophilicity of six statins namely; atorvastatin, simvastatin, pravastatin, lovastatin, rosuvastatin and fluvastatin is examined. A very good correlation between the chromatographically‐determined retention parameters (relative lipophilicity (RM0) or lipophilic parameter (C0)) and both experimental and computed log P values were obtained. However, the results indicate that the type of organic modifier in the mobile phase system (methanol, acetonitrile and acetone) has a small influence on RM0 or C0 values. Higher values of RM0 or C0 are ascribed to lipophilic statins and lower values of RM0 or C0 are attributed to hydrophilic ones. Therefore, RM0 or C0 could be effectively used as simple practical predictors of extra‐hepatic distributions of statins and thus their expected side effects. Furthermore, three QSPR (quantitative structure‐property relationship) models were constructed to describe the relationship between RM0 with log P and log D of the statins under investigation. These models can be very useful to predict the lipophilicity of other members of statin drugs and might be expanded to newly synthesized compounds with the same structural features.

The use of separation techniques in the analysis of some antiepileptic drugs: A critical review

ABSTRACT In the last few decades, many new antiepileptic drugs came out to medicine world, and their use was expanded over a wide range of cases. Analysts from all over the world developed many different separation methods for the determination of these drugs in a quantitative way either in pharmaceutical dosage forms or in biological fluids. In this review article, a summation of previously published separation methods including high-performance thin-layer chromatography, high-performance liquid chromatography, gas chromatography, and electrophoresis used for the determination of eslicarbazepine acetate, levetiracetam, lacosamide, oxcarbazepine, pregabalin, and retigabine are presented. These six drugs are the most commonly used drugs for the treatment of patients diagnosed with partial onset seizures. This article can help researchers and analysts to build upon this knowledge and add further methods of analysis in the future. GRAPHICAL ABSTRACT

Fabrication of novel electrochemical sensors based on modification with different polymorphs of MnO2 nanoparticles. Application to furosemide analysis in pharmaceutical and urine samples

A novel MnO2 nanoparticles/chitosan-modified pencil graphite electrode (MnO2 NPs/CS/PGE) was constructed using two different MnO2 polymorphs (γ-MnO2 and e-MnO2 nanoparticles). X-ray single phases of these two polymorphs were obtained by the comproportionation reaction between MnCl2 and KMnO4 (molar ratio of 5 : 1). The temperature of this reaction is the key factor governing the formation of the two polymorphs. Their structures were confirmed by powder X-ray diffraction (XRD), Fourier transform infrared (FTIR) and energy dispersive X-ray (EDX) analysis. 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 surface analysis of the modified electrodes. Compared to bare PGE, MnO2 NPs/CS/PGE shows higher effective surface area and excellent electrocatalytic activity towards the oxidation of the standard K3[Fe(CN)6]. The influence of different suspending solvents on the electrocatalytic activity of MnO2 was studied in detail. It was found that tetrahydrofuran (THF) is the optimum suspending solvent regarding the peak current signal and electrode kinetics. The results reveal that the modified γ-MnO2/CS/PGE is the most sensitive one compared to the other modified electrodes under investigation. The modified γ-MnO2/CS/PGE was applied for selective and sensitive determination of FUR. Under the optimized experimental conditions, γ-MnO2/CS/PGE provides a linear response over the concentration range of 0.05 to 4.20 μmol L−1 FUR with a low limit of detection, which was found to be 4.44 nmol L−1 (1.47 ng mL−1) for the 1st peak and 3.88 nmol L−1 (1.28 ng mL−1) for the 2nd one. The fabricated sensor exhibits a good reproducibility and selectivity and was applied successfully for the determination of FUR in its dosage forms and in spiked urine samples with good accuracy and precision.

Micelle and inclusion complex enhanced spectrofluorimetric methods for determination of Retigabine: Application in pharmaceutical and biological analysis

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.

Application of salting-out thin layer chromatography in computational prediction of minimum inhibitory concentration and blood-brain barrier penetration of some selected fluoroquinolones

Graphical abstract Figure. No caption available. HighlightsRetention behaviour of FQs was studied using SOTLC with ammonium sulphate mobile phase.Determination of lipophilicity parameters (RM0 or C0) of seven FQs.Experimentally‐determined lipophilicity values were correlated with those reported in databases.Principal component analysis was performed to explain differences among computational and experimental lipophilicity.QSAR and QSPR models (using RM0 or C0) values are generated as predictors for MIC and BBB penetration of FQs. ABSTRACT The 2017 FDA safety review regarding the CNS (central nervous system) side effects associated with the systemic use of fluoroquinolones antibacterials (FQs) was the key motivation to carry out this work. The main objective of this study is to investigate lipophilicity and retention parameters of some selected fluoroquinolones antibacterials (FQs) namely; levofloxacin (LEV), ofloxacin (OFL), gatifloxacin (GAT), norfloxacin (NOR), sparfloxacin (SPA), ciprofloxacin (CIP) and lomefloxacin (LOM) using salting‐out thin layer chromatography (SOTLC). Statistically significant correlations between the chromatographically‐obtained retention parameters and experimental log P values were found and expressed as quantitative structure retention relationship (QSRR) equations. Principal component analysis was carried out to explain the variation between chromatographic and both experimental and computed lipophilicity parameters. In another aspect of this study, a comparison between the chromatographically‐determined retention parameters (for five of the drugs under study) obtained using SOTLC (current study) and relative lipophilicity (RM0) determined using a previously reported RP (reversed‐phase)‐TLC method was carried out. Statistically significant correlation between the two methods was found, although RM0 values obtained using SOTLC was lower than those reported using RP‐TLC. Multiple linear regression analysis was performed to predict MIC (minimum inhibitory concentration) and blood brain barrier (BBB) penetration of the examined drugs in which efficient QSAR (quantitative structure‐activity relationship) and QSPR (quantitative structure‐property relationship) models were generated using the calculated chromatographic parameters (RM0 and C0). The described models can provide a useful approach to predict MIC and BBB penetration of newly synthesized FQs targeting to increase their activity against Gram‐positive organisms and to minimize the associated CNS side effects.

Utility of Ionic Liquid-based Surfactant in Enhancement of Oxidation Peak Signal of Atorvastatin at Pencil Graphite Electrode

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).

ε-MnO2-modified graphite electrode as a novel electrochemical sensor for the ultrasensitive detection of the newly FDA approved Hepatitis C antiviral drug ledipasvir

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 (γ- 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 γ-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 γ- 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 0.025-3.60 μmol L-1 LED with a low limit of detection, which was found to be 5.10 nmol L-1 (4.50 ng mL-1) for the 1st peak and 9.20 nmol L-1 (8.10 ng mL-1) for the 2nd one. In addition, the oxidation behavior of LED is discussed with a full investigation of the oxidized product using FT-IR and LC/MS. The fabricated sensor exhibits a good precision, selectivity and stability and was applied successfully for the determination of LED in its tablets and real rat plasma samples with a good recovery using a simple extraction technique.