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

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

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

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

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

Protective Role of Quercetin in Carbon Tetrachloride Induced Toxicity in Rat Brain: Biochemical, Spectrophotometric Assays and Computational Approach

Carbon tetrachloride (CCL4) induces oxidative stress by free radical toxicities, inflammation, and neurotoxicity. Quercetin (Q), on the other hand, has a role as anti-inflammatory, antioxidant, antibacterial, and free radical-scavenging. This study explored protection given by quercetin against CCL4 induced neurotoxicity in rats at given concentrations. Male Wistar rats were divided into four groups Group C: control group; Group CCL4: given a single oral dose of 1 mL/kg bw CCL4; Group Q: given a single i.p injection of 100 mg/kg bw quercetin; and Group Q + CCL4: given a single i.p injection of 100 mg/kg bw quercetin before two hours of a single oral dose of 1 mL/kg bw CCL4. The results from brain-to-body weight ratio, morphology, lipid peroxidation, brain urea, ascorbic acid, reduced glutathione, sodium, and enzyme alterations (aspartate aminotransferase (AST), alanine aminotransferase (ALT), catalase, and superoxide dismutase) suggested alterations by CCL4 and a significant reversal of these parameters by quercetin. In silico analysis of quercetin with various proteins was conducted to understand the molecular mechanism of its protection. The results identified by BzScore4 D showed moderate binding between quercetin and the following receptors: glucocorticoids, estrogen beta, and androgens and weak binding between quercetin and the following proteins: estrogen alpha, Peroxisome proliferator-activated receptors (PPARγ), Herg k+ channel, Liver x, mineralocorticoid, progesterone, Thyroid α, and Thyroid β. Three-dimensional/four-dimensional visualization of binding modes of quercetin with glucocorticoids, estrogen beta, and androgen receptors was performed. Based on the results, a possible mechanism is hypothesized for quercetin protection against CCL4 toxicity in the rat brain

New ultra-performance liquid chromatography-tandem mass spectrometry method for the determination of irbesartan in human plasma

With the objective of reducing analysis time and maintaining good efficiency, there has been substantial focus on high-speed chromatographic separations and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is a preeminent analytical tool for rapid biomedical analysis. In this study a simple, rapid, sensitive, and specific ultra-performance liquid chromatography-MS/MS method was developed and validated for quantification of the angiotensin II receptor antagonist, irbesartan (IRB), in human plasma. After a simple protein precipitation using methanol and acetonitrile, IRB and internal standard (IS) telmisartan were separated on Acquity UPLC BEH C18 column (50 mm × 2.1 mm, i.d. 1.7 μm, Waters, Milford, MA, USA) using a mobile phase consisted of acetonitrile: methanol: 10 mM ammonium acetate (70: 15: 15 v/v/v) with a flow rate of 0.4 mL/min and detected MS/MS in negative ion mode. The ion transitions recorded in multiple reaction monitoring mode were m/z 427.2→193.08 for IRB and m/z 513.2→469.3 for IS. The assay exhibited a linear dynamic range of 2–500 ng/mL for IRB in human plasma with good correlation coefficient of (0.995) and with a lower limit of quantitation of 2 ng/mL. The intra- and interassay precisions were satisfactory; the relative standard deviations did not exceed 9.91%. The proposed UPLC-MS/MS method is simple, rapid, and highly sensitive, and hence it could be reliable for pharmacokinetic and toxicokinetic study in both animals and humans