Simple, sensitive and rapid determination of linifanib (ABT-869), a novel tyrosine kinase inhibitor in rat plasma by UHPLC-MS/MS

An overall model for sulfur self-retention in ash during coal particle combustion is developed in this paper. It is assumed that sulfur retention during char combustion occurs due to the reaction between SO2 and CaO in the form of uniformly distributed non-porous grains. Parametric analysis shows that the process of sulfur self-retention is limited by solid difussion through the non-porous product layer formed on the CaO grains and that the most important coal characteristics which influence sulfur self-retention are coal rank. content of sulfur forms. molar Ca/S ratio and particle radius. A comparison with the experimentally obtained values in a FB reactor showed that die model can adequately predict the kinetics of the process, the levels of the obtained values of the SSR efficiencies, as well as the influence of temperature and coal particle size.U radu je prikazan razvijeni model zadržavanja sumpora u pepelu tokom sagorevanja uglja. Pretpostavka modela je da se zadržavanje sumpora tokom sagorevanja koksnog ostatka odigrava usled reakcije SO2 i CaO koji je u obliku ravnomerno raspoređenih zrna. Parametarska analiza je pokazala da je proces zadržavanja sumpora kontrolisan difuzijom kroz formirani sloj čvrstog produkta na zrnima CaO, kao i da su rang uglja, sadržaj formi sumpora molarni Ca/S odnos i veličina čestice važne osobine uglja koje utiču na proces. Poređenje sa eksperimentalnim rezultatima dobijenim u reaktoru sa fluidizovanim slojem je pokazalo da model može adekvatno da predvidi kinetiku procesa, efikasnost zadržavanja sumpora u pepelu, kao i uticaj temperature i veličine čestice uglja

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

A Study of Thermodynamic Properties of Transition Metal Diborides

AbstractThe diborides are members of a broad class of materials known as the boron-rich solids, which consist of extended networks of covalently bonded boron (B) atoms stabilized through donation of electrons from the metal atoms. Although the structures of the diborides are unique, their physical properties are somewhat similar to those of nitrides and carbides; they are extremely hard and have very high melting points. They are attractive for the same types of applications as super hard, refractory materials, such as in composites and in hard coatings. The proposal presents an overview of some of the important properties of transition metal diborides (TMB2), as these are of interest for fundamental reasons as well as for practical applications. Keywords: TMB2; AlB2; Physical propertie

A spectroscopic, thermodynamic and molecular docking study of the binding mechanism of dapoxetine with calf thymus DNA

Dapoxetine is a selective serotonin reuptake inhibitor, used to treat premature ejaculation in men. Dapoxetine may interact with theDNAand hence this study investigated dapoxetine and calf thymusDNA(ctDNA) binding interaction. The interaction study of ligands to DNA is of importance in the development of molecular probes and therapeutic agents. Spectroscopic techniques including spectrofluorometry and spectrophotometry were employed to study this interaction. Fluorescence studies indicated a static quenching mechanism between dapoxetine and ctDNA. Groove binding was suggested as the mode of interaction between dapoxetine and ctDNA based onUVabsorption, circular dichroism (CD) spectroscopy, iodide quenching and molecular docking studies. The studies conducted at three different temperatures 298, 303 and 310 K indicated a strong binding interaction at higher temperatures. Thermodynamic studies conducted indicated involvement of hydrophobic interaction between ctDNA and dapoxetine and were entropy-driven. Ethidium bromide probe study suggested that dapoxetine does not bind to ctDNA in an intercalative fashion. Iodide quenching studies further proved the non-intercalative binding of ctDNA with dapoxetine. Ionic strength studies conducted ruled out the electrostatic binding mechanism between ctDNA and dapoxetine. Molecular docking analysis performed for the dapoxetine with calf thymus DNA (ctDNA) interaction and confirmed minor groove binding of dapoxetine to ctDNA. The study helped to reveal the binding interaction mechanism between dapoxetine and ctDNA

Pressure-volume Relationship for Platinum and Aluminium

Platinum and Aluminium are widely used as a pressure calibration standard. The present proposal which intends to compare the efficiency of the four equations under close examination reports the V/VO versus P values derived from the new modified forms of Murnaghan equation NMME1, NMME2, Birch equation (BE) and Freund-Ingalls (FIE) obtained for the best agreement with the experimental data of Mc Queen et.al

Theoretical study of the antioxidant mechanism and structure-activity relationships of 1,3,4-oxadiazol-2-ylthieno[2,3-d]pyrimidin-4-amine derivatives: a computational approach

A theoretical thermodynamic study was conducted to investigate the antioxidant activity and mechanism of 1,3,4-oxadiazol-2-ylthieno[2,3-d]pyrimidin-4-amine derivatives (OTP) using a Density Functional Theory (DFT) approach. The study assessed how solvent environments influence the antioxidant properties of these derivatives. With the increasing prevalence of diseases linked to oxidative stress, such as cancer and cardiovascular diseases, antioxidants are crucial in mitigating the damage caused by free radicals. Previous research has demonstrated the remarkable scavenging abilities of 1,3,4-oxadiazole derivatives, prompting this investigation into their potential using computational methods. DFT calculations were employed to analyze key parameters, including bond dissociation enthalpy (BDE), ionization potential (IP), proton dissociation enthalpy (PDE), and electron transfer enthalpy (ETE), to delineate the antioxidant mechanisms of these compounds. Our findings indicate that specific electron-donating groups such as amine on the phenyl rings significantly enhance the antioxidant activities of these derivatives. The study also integrates global and local reactivity descriptors, such as Fukui functions and HOMO-LUMO energies, to predict the stability and reactivity of these molecules, providing insights into their potential as effective synthetic antioxidants in pharmaceutical applications

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

Influence of Rutin, Sinapic Acid, and Naringenin on Binding of Tyrosine Kinase Inhibitor Erlotinib to Bovine Serum Albumin Using Analytical Techniques Along with Computational Approach

Flavonoid-containing food supplements are widely used as antioxidants, and the continuous use of these supplements with other drugs can lead to clinically significant interactions between these and other drugs. The medications in systemic circulation are mainly transported by serum albumin, a major transport protein. This study evaluated the interactions of rutin (RUT), naringenin (NAR), and sinapic acid (SIN) with the most abundant transport protein, bovine serum albumin (BSA), and the anticancer drug, the tyrosine kinase inhibitor Erlotinib (ETB), using various analytical methods. Interaction between multiple types of ligands with the transport proteins and competition between themselves can lead to the bound ETB’s displacement from the BSA-binding site, leading to elevated ETB concentrations in the systemic circulation. These elevated drug fractions can lead to adverse events and lower tolerance, and increased resistance to the therapeutic regimen of ETB. The experimental and computational methods, including molecular-docking studies, were used to understand the molecular interactions. The results suggested that the complexes formed were utterly different in the binary and the ternary system. Furthermore, comparing the ternary systems amongst themselves, the spectra differed from each other. They thus inferred that complexes formed between BSA-ETB in the presence of each RUT, NAR, and SIN separately were also different, with the highest value of the reduction in the binding energy in RUT, followed by SIN and then NAR. Thus, we conclude that a competitive binding between the ETB and these flavonoids might influence the ETB pharmacokinetics in cancer patients by increasing ETB tolerance or resistance

Interaction Characterization of a Tyrosine Kinase Inhibitor Erlotinib with a Model Transport Protein in the Presence of Quercetin: A Drug–Protein and Drug–Drug Interaction Investigation Using Multi-Spectroscopic and Computational Approaches

The interaction between erlotinib (ERL) and bovine serum albumin (BSA) was studied in the presence of quercetin (QUR), a flavonoid with antioxidant properties. Ligands bind to the transport protein BSA resulting in competition between different ligands and displacing a bound ligand, resulting in higher plasma concentrations. Therefore, various spectroscopic experiments were conducted in addition to in silico studies to evaluate the interaction behavior of the BSA-ERL system in the presence and absence of QUR. The quenching curve and binding constants values suggest competition between QUR and ERL to bind to BSA. The binding constant for the BSA-ERL system decreased from 2.07 × 104 to 0.02 × 102 in the presence of QUR. The interaction of ERL with BSA at Site II is ruled out based on the site marker studies. The suggested Site on BSA for interaction with ERL is Site I. Stability of the BSA-ERL system was established with molecular dynamic simulation studies for both Site I and Site III interaction. In addition, the analysis can significantly help evaluate the effect of various quercetin-containing foods and supplements during the ERL-treatment regimen. In vitro binding evaluation provides a cheaper alternative approach to investigate ligand-protein interaction before clinical studies