Enhanced spectrofluorimetric determination of the multitargeted tyrosine kinase inhibitor, crizotinib, in human plasma via micelle-mediated approach

Purpose: To quantify the multi-targeted tyrosine kinase inhibitor, crizotinib, in human plasma and bulk powder by highly sensitive micellar enhanced spectrofluorimetric procedure.Method: The developed procedure was based on measuring the fluorescence intensity of crizotinib (CRZ) in sodium dodecyl sulphate (SDS) micellar system at 404 nm after excitation at 271 nm. Validation of the developed procedure was carried out following ICH (International Council for Harmonization) guidelines.Results: Maximum fluorescence intensity (FI) was attained by addition of 0.2 mL SDS and 0.2 mL HCl (1N) to CRZ aliquots and then dilution with distilled water. There was a linear relationship between the FI of CRZ and its concentration over the range, 5 – 400 ng/mL, with limit of detection and of quantification of 1.857 and 5.628 ng/mL respectively. The developed procedure was successfully applied to assay CRZ in pure powder form and spiked human plasma with mean recovery of 100.68 ± 0.37 and 99.98 ± 0.20 %, respectively.Conclusion: The developed procedure is simple and sensitive, and can be applied to routine analysis of CRZ in pure powder form as well as in clinical laboratories for the determination of CRZ in plasma.Keywords: Crizotinib, Spectrofluorimetry, Micelle, Human plasma, Sodium dodecyl sulphat

Water Absorption Enhancement Of Sodium Poly Acrylate And Poly(2-Acrylamido-2-Methylpropane Sulphonic Acid) Based Hydrogel Mixtures

Introduction: Hydrogels are hydrophilic polymers which are cross-linked to form three-dimensional structures, which can absorb, swell and retain huge amounts of water or aqueous fluids. Objective: This paper reports the preparation and characterization of Poly (2-Acrylamido-2-Methylpropane Sulphonic Acid) (PAMPS) hydrogel with different crosslinking intensities. Methodology: 2-Acrylamido-2-methylpropane sulfonic acid (AMPS) monomer was purchased from Alfa Aesar Company as reagent grade. It was used as received (\u3e98% purity) without any further purification. PAMPS hydrogel was prepared by free radical crosslinking solution polymerization of AMPS in water at room temperature under a nitrogen blanket in cylindrical glass tubes. The characteristics of the obtained PAMPS hydrogel were compared with those of commercial sodium polyacrylates hydrogel. Results: It was found that decreasing the crosslinker weight improved the absorbance capacity but to a limit. The suggested reasons were discussed. The mixture showed higher absorbance rate than PAMPS, and bigger absorbance capacity than sodium polyacrylates. Conclusion: This paper investigates the effect of crosslinker ratio on the swelling capacity of PAMPS. It was found that as the crosslinking ratio decreases, the porosity of the hydrogel increases, thus improving the swelling capacity

ICH guidelines-compliant HPLC-UV method for pharmaceutical quality control and therapeutic drug monitoring of the multi-targeted tyrosine kinase inhibitor pazopanib

In this study, an HPLC method with ultraviolet (UV) detection was developed and validated for determination of pazopanib (PAZ), a multi-targeted tyrosine kinase (TK) inhibitor in bulk drug, tablets formulation, and in human plasma. Oxamniquine (OXA) was used as internal standard (IS). The analytical column used for the separation was Nucleosil CN with dimensions (i.d. 250 × 4.6 mm and particle size 5 μm). The separation was carried out in isocratic mode with mobile phase constituting acetonitrile:100 mM sodium acetate buffer (pH 4.5); 40:60, v/v. The developed method was linear in the concentration range of 2–12 μg mL–1 and had a correlation coefficient (r = 0.9998, n = 6). The limits of detection and quantitation (LOD and LOQ) were 0.27 and 0.82 μg mL–1, respectively. The relative standard deviations for the inter- and intra-assay precisions were below 3.61 % and the accuracy of the method was 96.69–104.15 %. The degradation products were resolved from the intact drug, proving the stability-indicating property of the proposed method. The recovery values were 100.17–103.98 % (± 1.81–4.02) for determination of PAZ in human plasma. The results indicated the versatility of the new method in estimation of PAZ during pharmaceutical quality control (QC) and therapeutic drug monitoring (TDM).Keywords: Tyrosine kinase inhibitors, pazopanib, HPLC, UV detection, quality control, therapeutic drug monitorin

Selective Spectrophotometric and Spectrofluorometric Methods for the Determination of Amantadine Hydrochloride in Capsules and Plasma via Derivatization with 1,2-Naphthoquinone-4-sulphonate

New selective and sensitive spectrophotometric and spectrofluorometric methods have been developed and validated for the determination of amantadine hydrochloride (AMD) in capsules and plasma. The methods were based on the condensation of AMD with 1,2-naphthoquinone-4-sulphonate (NQS) in an alkaline medium to form an orange-colored product. The spectrophotometric method involved the measurement of the colored product at 460  nm. The spectrofluorometric method involved the reduction of the product with potassium borohydride, and the subsequent measurement of the formed fluorescent reduced AMD-NQS product at 382  nm after excitation at 293  nm. The variables that affected the reaction were carefully studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9972–0.9974) and low LOD (1.39 and 0.013 μg mL−1) were obtained in the ranges of 5–80 and 0.05–10  μg mL−1 for the spectrophotometric and spectrofluorometric methods, respectively. The precisions of the methods were satisfactory; RSD ≤2.04%. Both methods were successfully applied to the determination of AMD in capsules. As its higher sensitivity, the spectrofluorometric method was applied to the determination of AMD in plasma; the recovery was 96.3–101.2 ± 0.57–4.2%. The results obtained by the proposed methods were comparable with those obtained by the official metho

Polymorphism of growth hormone gene and its association with wool traits in Egyptian sheep breeds

Growth hormone (GH) gene has been described as a candidate gene for marker-assisted selection in different farm animals. The present study was designed to identify the polymorphism in GH gene and its association with variation of wool traits in Egyptian sheep breeds. Wool and blood samples were collected from 42 animals including two breeds (Barki and Rahmani) and one crossbred (Rahmani x Awase). Measurements of wool traits were analyzed and involved staple strength (Str), staple length (STL), fiber diameter (FD) and clean fleece yield (CFW). DNA was extracted from blood samples and a 365-bp fragment from exon V was amplified by polymerase chain reaction (PCR). Single strand conformation polymorphisim (SSCP) analysis showed two conformational patterns. The pattern I was recorded to be more frequent (83.3, 92.86 and 90%) than pattern II (16.7, 7.14 and 10%) in Barki, Rahmani and crossbred, respectively. The sequence analysis showed one single nucleotide polymorphism (C/T). The pattern I (allele T) has been found to affect CFW and FD than pattern II (allele C). Whereas, C allele was more pronounced for Str and STL. These traits are the most important parameters determining commercial values of wool that are preferred for clothing or carpets industry. The nucleotide sequences of C and T alleles were submitted to GenBank and have the accession numbers: KT250511 and KT250512, respectively. In conclusion, the present results provide evidence that there is a single nucleotide polymorphism within GH gene in Egyptian sheep breeds. This mutation was found to have some effects on wool traits. Therefore our data show interesting prospects in future selection programs for improving wool industry.Key words: Sheep, wool, growth hormone (GH) gene, polymorphism, single strand conformation polymorphism (SSCP)

New Spectrophotometric and Fluorimetric Methods for Determination of Fluoxetine in Pharmaceutical Formulations

New simple and sensitive spectrophotometric and fluorimetric methods have been developed and validated for the determination of fluoxetine hydrochloride (FLX) in its pharmaceutical formulations. The spectrophotometric method was based on the reaction of FLX with 1,2-naphthoquinone-4-sulphonate (NQS) in an alkaline medium (pH 11) to form an orange-colored product that was measured at 490 nm. The fluorimetric method was based on the reaction of FLX with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in an alkaline medium (pH 8) to form a highly fluorescent product that was measured at 545 nm after excitation at 490 nm. The variables affecting the reactions of FLX with both NQS and NBD-Cl were carefully studied and optimized. The kinetics of the reactions were investigated, and the reaction mechanisms were presented. Under the optimum reaction conditions, good linear relationships were found between the readings and the concentrations of FLX in the ranges of 0.3–6 and 0.035–0.5 μg mL−1 for the spectrophotometric and fluorimetric methods, respectively. The limits of detection were 0.1 and 0.01 μg mL−1 for the spectrophotometric and fluorimetric methods, respectively. Both methods were successfully applied to the determination of FLX in its pharmaceutical formulations

Simple Spectrophotometric Method for Determination of Paroxetine in Tablets Using 1,2-Naphthoquinone-4-Sulphonate as a Chromogenic Reagent

Simple and rapid spectrophotometric method has been developed and validated for the determination of paroxetine (PRX) in tablets. The proposed method was based on nucleophilic substitution reaction of PRX with 1,2-naphthoquinone-4-sulphonate (NQS) in an alkaline medium to form an orange-colored product of maximum absorption peak (λmax) at 488 nm. The stoichiometry and kinetics of the reaction were studied, and the reaction mechanism was postulated. Under the optimized reaction conditions, Beer's law correlating the absorbance (A) with PRX concentration (C) was obeyed in the range of 1–8 μg mL−1. The regression equation for the calibration data was: A = 0.0031 + 0.1609 C, with good correlation coefficients (0.9992). The molar absorptivity (ε) was 5.9 × 105 L mol−1 1 cm−1. The limits of detection and quantitation were 0.3 and 0.8 μg mL−1, respectively. The precision of the method was satisfactory; the values of relative standard deviations did not exceed 2%. The proposed method was successfully applied to the determination of PRX in its pharmaceutical tablets with good accuracy and precisions; the label claim percentage was 97.17 ± 1.06 %. The results obtained by the proposed method were comparable with those obtained by the official method

Temperature Dependence of GaN HEMT Small Signal Parameters

This study presents the temperature dependence of small signal parameters of GaN/SiC HEMTs across the 0–150°C range. The changes with temperature for transconductance (m), output impedance (ds and ds), feedback capacitance (dg), input capacitance (gs), and gate resistance (g) are measured. The variations with temperature are established for m, ds, ds, dg, gs, and g in the GaN technology. This information is useful for MMIC designs

Novel microwell-based spectrophotometric assay for determination of atorvastatin calcium in its pharmaceutical formulations

The formation of a colored charge-transfer (CT) complex between atorvastatin calcium (ATR-Ca) as a n-electron donor and 2, 3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as a π-electron acceptor was investigated, for the first time. The spectral characteristics of the CT complex have been described, and the reaction mechanism has been proved by computational molecular modeling. The reaction was employed in the development of a novel microwell-based spectrophotometric assay for determination of ATR-Ca in its pharmaceutical formulations. The proposed assay was carried out in 96-microwell plates. The absorbance of the colored-CT complex was measured at 460 nm by microwell-plate absorbance reader. The optimum conditions of the reaction and the analytical procedures of the assay were established. Under the optimum conditions, linear relationship with good correlation coefficient (0.9995) was found between the absorbance and the concentration of ATR-Ca in the range of 10-150 μg/well. The limits of detection and quantitation were 5.3 and 15.8 μg/well, respectively. No interference was observed from the additives that are present in the pharmaceutical formulation or from the drugs that are co-formulated with ATR-Ca in its combined formulations. The assay was successfully applied to the analysis of ATR-Ca in its pharmaceutical dosage forms with good accuracy and precision. The assay described herein has great practical value in the routine analysis of ATR-Ca in quality control laboratories, as it has high throughput property, consumes minimum volume of organic solvent thus it offers the reduction in the exposures of the analysts to the toxic effects of organic solvents, and reduction in the analysis cost by 50-fold. Although the proposed assay was validated for ATR-Ca, however, the same methodology could be used for any electron-donating analyte for which a CT reaction can be performed