Ramadan Ali

A facile synthesis of 3D NiFe2O4 nanospheres anchored on a novel ionic liquid modified reduced graphene oxide for electrochemical sensing of ledipasvir: Application to human pharmacokinetic study

Novel and sensitive electrochemical sensor was fabricated for the assay of anti-HCV ledipasvir (LEDV) in different matrices. The designed sensor was based on 3D spinel ferromagnetic NiFe2O4 nanospheres and reduced graphene oxide (RGO) supported by morpholinium acid sulphate (MHS), as an ionic liquid (RGO/NSNiFe2O4/MHS). This sensor design was assigned to synergistically tailor the unique properties of nanostructured ferrites, RGO, and ionic liquid to maximize the sensor response. Electrode modification prevented aggregation of NiFe2O4, increasing electroactive surface area and allowed remarkable electro-catalytic oxidation of LEDV with an enhanced oxidation response. Differential pulse voltammetry was used for detection LEDV in complex matrices whereas; cyclic voltammetry and other techniques were employed to characterize the developed sensor properties. All experimental factors regarding sensor fabrication and chemical sensing properties were carefully studied and optimized. Under the optimum conditions, the designated sensor displayed a wide linear range (0.4-350 ng mL-1) with LOD of 0.133 ng mL-1. Additionally, the proposed sensor demonstrated good selectivity, stability and reproducibility, enabling the quantitative detection of LEDV in Harvoni® tablets, human plasma and in a pharmacokinetic study. Our findings suggest that the developed sensor is a potential prototype material for fabrication of high-performance electrochemical sensors.

Enhanced dispersive solid phase extraction assisted by cloud point strategy prior to fluorometric determination of anti-hepatitis C drug velpatasvir in pharmaceutical tablets and body fluids

An innovative spectrofluorometric method was developed for the analysis of a recently FDA approved anti-hepatitis C velpatasvir (VELP). The developed method was relied on dispersive solid phase extraction (dSPE) using synergistic effect of reduced graphene oxide (RGO) and cobalt hydroxide nanoparticles (CHNPs) in addition to cloud point extraction (CPE) using polyethylene glycol 6000 (PEG 6000) as non-ionic surfactant. This method combines the merits of preconcentration and interferences elimination achieved by dSPE and CPE, respectively. All relevant parameters such as surfactant concentration, ionic strength, pH, incubation time and others were thoroughly investigated and optimized. Fluorometric detection of VELP was carried out at excitation wavelength of 350 nm and emission wavelength of 415 nm. Under the optimum conditions, a linear calibration curve was achieved in the range of 0.5–45 ng mL−1. Limits of detection (LOD) and quantification (LOQ) based on three and ten times the standard deviation of the blank were 0.040 and 0.112 ng mL−1, respectively. This method was successfully applied for determination of VELP in real samples such as tablets, human plasma and urine samples with good recoveries.

Sensitive Spectrofluorimetric Protocol for the Determination of Fluoxetine and Paroxetine Through Binary Complex Formation with Eosin Y

abstract A spectrofluorometric procedure was developed and fully validated for simple and sensitive determination of two antidepressant drugs; fluoxetine hydrochloride and paroxetine hydrochloride, in their pure forms and pharmaceutical formulations. The method is based on a binary complex formation with eosin Y in the presence of Teorell - Stenhagen buffer at pH 3.0. The quenching of the native fluorescence of eosin Y due to complex formation with the studied drugs was measured in the aqueous solution without extraction at 545 nm after excitation at 301 nm. At the optimum reaction conditions, the calibration graphs between the fluorescence quenching values (ΔF) and the drug concentrations were rectilinear over the ranges of 0.2–2.4 and 0.1–2.4 μg mL −1 for fluoxetine and paroxetine respectively. The proposed method was successfully applied for the determination of the studied drugs in pharmaceutical formulations without interference from the common excipients.

Synthesis of Fe3O4 nanobead-functionalized 8-hydroxyquinoline sulfonic acid supported by an ion-imprinted biopolymer as a recognition site for Al3+ ions: estimation in human serum and water samples

Herein, a novel “turn on” ion-imprinted chemosensor for highly sensitive and selective detection of Al3+ ions in complex matrices has been developed. The method was based on using chitosan (CHIT) biopolymer/magnetite nanoparticles (MGNPs) functionalized with 8-hydroxyquinoline sulfonic acid (8-HQS) in the presence of Al3+ ions to synthesize a magnetite ion non-imprinted biopolymer (MGINIBP) chemosensor. This newly developed chemosensor was synthesized via polymerization of CHIT with [3-(2,3-epoxypropoxy)-propyl]trimethoxysilane [EPPTMS] in the presence of magnetite nanoparticles, 8-HQS, and an Al3+ ion template. The template was then removed from the sensor using 0.5 M NaF to form new recognition sites for Al3+. The newly developed chemosensor was termed as a magnetite ion-imprinted biopolymer (MGIIBP). Exposure of Al3+ ions to the developed system embedded with 8-HQS resulted in the formation of a fluorescent polymer, and emission maximum was obtained at 500 nm after excitation at 365 nm. Furthermore, with the increasing Al3+ ion concentration, the fluorescence intensity increases within the range 0.081–9.0 × 10−8 M with a limit of detection (LOD) of 0.027 × 10−8 M. In addition, the synthesized chemosensor was characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FTIR). The proposed MGIIBP sensor was successfully applied to the determination of Al3+ ions in water and human serum samples as model examples of complex natural matrix media.

Micellar spectrofluorimetric protocol for the innovative determination of HCV antiviral (daclatasvir) with enhanced sensitivity: Application to human plasma and stability study

Daclatasvir dihydrochloride (DAC) is a new, direct-acting antiviral drug with powerful inhibitory effect against all hepatitis C virus (HCV) genotypes. A sensitive, simple, fast and specific fluorometric method for estimation of DAC in the presence of sofosbuvir was developed and validated. The method is based on reinforcement the fluorescence intensity of DAC by 170% of its original value in an aqueous solution of hexadecyl trimethyl ammonium bromide (pH 5.5, Teorell and Stenhagen buffer). The fluorescence intensity measurements were accomplished at 387 nm with 328 nm for excitation wavelength. A linear relationship was achieved between the DAC concentration and the fluorescence intensity in a range of 50.0-2000.0 ng ml-1 with 0.9998 and 0.9999 for the determination and correlation coefficients, respectively. The detection and quantitation limits were 13.4, 40.8 ng ml-1, respectively. The excellent sensitivity and specificity of the proposed method allowed the efficient estimation of DAC in real human plasma with adequate recovery (81.78 ± 1.57), and the selective determination for DAC in its commercial dosage form without interference from tablet excipient. Moreover, the proposed method was expanded to examine the stability of DAC by determination the parent drug of DAC in the presence of its oxidative, alkaline, acidic, UV, daylight and sunlight degradations products in agreement with ICH guidelines. Furthermore, the kinetic study of acidic and oxidative degradations of DAC was inspected. In addition, the half-life times of the reaction (t1/2) and the first-order reaction rate constants were estimated. Moreover, a suggestion for the degradation pathway was supposed.

Specific stability indicating spectrofluorimetric method for determination of ledipasvir in the presence of its confirmed degradation products; application in human plasma

A rapid and specific spectrofluorimetric method with higher sensitivity was developed for determination of ledipasvir (LDS) in tablets and human plasma. The proposed method relies on hydrogen bonding formations between the hydroxyl groups of polyoxyethylene 50 stearate and LDS, causing significant enhancement of its native fluorescence. The fluorescence intensity was measured at 430 nm after excitation at 340 nm. The fluorescence-concentration plot was rectilinear over the range 1-400 ng mL-1 with detection and quantification limits of 0.25 and 1.10 ng mL-1, respectively. The high sensitivity of the proposed method permits its application for ledipasvir determinations in real human plasma even in the presence of co-administered drugs sofosbuvir and ribavirin. Moreover, the proposed method was further extended to stability studies of ledipasvir after exposure to different forced degradation conditions according to ICH guidelines, along with the structural elucidation of its degradation products utilizing IR and Mass spectra. A proposal for the degradation pathways was presented.

Facile complexation reactions for the selective spectrofluorimetric determination of albendazole in oral dosage forms and spiked human plasma

Two simple, sensitive, and rapid spectrofluorimetric methods were developed and validated for the determination of albendazole. The first method (method I) was based on the quenching effect of albendazole on the native fluorescence of erythrosine B. The fluorescence intensity was measured at 554 nm after extraction at 527 nm. In the second method (method II) the drug was reacted with lanthanum(III) ions to form a metal complex, which was measured at 340 nm after excitation at 295 nm. The suitable pH was 3.4 (Teorell–Stenhagen buffer) and pH 5.5 (phosphate buffer solution), for method I and II, respectively. The influence of experimental factors on the fluorescence intensity of the reaction products was investigated and optimized. The linear concentration ranges were 0.2–3.5 and 0.06–0.90 μg mL−1, with detection limits of 0.049 and 0.019 μg mL−1 for method I and II, respectively. ICH guidelines were followed for validation of the developed procedures, and the results were acceptable. The Gibbs free energy change of the reactions was −24.6 and −27.5 kJ mol−1 for method I and II, respectively. These negative values indicated the high feasibility of these reactions at ambient temperature. The proposed procedures were applied successfully for the determination of albendazole in commercial dosage forms and spiked human plasma. The results showed high precision, accuracy and recovery of the reported methods without any significant interference from pharmaceutical excipients or plasma components.

Solid-State FTIR Spectroscopic Study of Two Binary Mixtures: Cefepime-Metronidazole and Cefoperazone-Sulbactam

The structural information of the pharmaceuticals and insights on the modes of molecular interactions are very important aspects in drug development. In this work, two cephalosporins and antimicrobial combinations, cefepime-metronidazole and cefoperazone-sulbactam, were studied in the solid state using FTIR spectroscopy for the first time. Quantitation of the studied drugs and their binary mixtures was performed by integrating the peak areas of the characteristic well-resolved bands: υ (C=O) band at 1773 cm−1 for cefepime and ring torsion band at 826 cm−1 for metronidazole and υ (C=O) band at 1715 cm−1 for cefoperazone and ring torsion band at 1124 cm−1 for sulbactam. The results of this work were compared with the relevant spectrophotometric reported methods. This study provides data that can be used for the preparative process monitoring of the studied drugs in various dosage forms.

Spectroscopic Analysis and Antibacterial Evaluation of Certain Third Generation Cephalosporins Through Metal Complexation

Abstract Metal complexes of cefixime, cefpodoxime and cefperazone with aluminium, calcium, strontium and zinc have been synthesized and characterized with melting points, UV-Visible and FTIR spectroscopy. The in vitro evaluation of the antimicrobial activity has revealed a significant reduction of the activity for most of the prepared metals complexes. Furthermore, the complex with zinc (II) has been utilized for the determination of the studied cephalosporins using atomic absorption spectroscopy for the first time. The method showed linear concentration ranges of 0.51 – 13, 0.56 – 15, and 1.25 – 20 μg mL-1 for cefixime, cefpodoxime and cefoperazone, respectively with correlation coefficient not less than 0.9996. LODs of the proposed method were 0.17, 0.19 and 0.41 μg mL-1 respectively. The method was successfully applied for the determination of the studied drugs in their commercially available dosage forms with good precision and accuracy.