Simultaneous determination of simvastatin and simvastatin acid in human plasma by LC-MS/MS without polarity switch: application to a bioequivalence study

A simple, specific and sensitive LC-MS/MS assay for simultaneous determination of simvastatin (SV) and its active beta-hydroxy acid metabolite, simvastatin acid (SVA) in human plasma was developed using a statin analog as internal standard (IS). The method was validated over a dynamic linear range of 0.20-100.00 ng/mL for SV and 0.10-50.00 ng/mL for SVA with correlation coefficient r > or = 0.9987 and 0.9989, respectively. The analytes and IS were extracted from 500 microL aliquots of human plasma via liquid-liquid extraction using methyl tert-butyl ether and separated through an Aquasil C18 column (100 mm x 2.1 mm, 5 microm). Detection of analytes and IS was done by MS/MS with a turbo ion spray interface operating in positive ion and selective reaction monitoring acquisition mode. The total chromatographic run time was 3.0 min. Flash freezing of the aqueous phase was an added advantage during liquid-liquid extraction, which considerably reduced time and labour. The method was extensively validated for its accuracy, precision, recovery, stability studies and matrix effect. The method was successfully used for bioequivalence study of 40 mg SV tablet formulation in 12 human subjects under fasting condition.     

Nanostructured Cu and Cu@Cu(2)O core shell catalysts for hydrogen generation from ammonia-borane

Copper nanoparticles have been prepared by the solvated metal atom dispersion (SMAD) method. Oxidation of the SMAD prepared copper colloids resulted in Cu@Cu(2)O core shell structures (7.7 +/- 1.8 nm) or Cu(2)O nanoparticles depending on the reaction conditions. The nano Cu, Cu@Cu(2)O core shell, and Cu(2)O particles were found to be catalytically active for the generation of hydrogen from ammonia-borane either via hydrolysis or methanolysis reaction.     

Dendronized polystyrene via orthogonal double‐click reactions

Dendronized copolymers bearing two different dendrons as side chains have been synthesized using a modular orthogonal “double‐click” reaction based strategy. The orthogonality of the Huisgen‐type azide‐alkyne cycloaddition and the Diels–Alder reaction was utilized to attach different dendrons to the polymer backbone via the “graft‐to” strategy. First through third generations of polyaryl ether dendrons appended with an alkyne group and polyester dendrons possessing a furan‐protected maleimide group at their focal point were reacted with a styrene based copolymer containing azide and anthracene moieties as side chains. The efficiency and selectivity of the orthogonal dendronization of the copolymers were examined via various analytical methods such as ¹H NMR spectroscopy, FTIR and gel permeation chromatography. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 5029–5037     

Multiarm star polymers with peripheral dendritic PMMA arms through Diels–Alder click reaction

Dendritic 2‐ and 4‐arm PMMA‐based star polymers with furan‐protected maleimide at their focal point, (PMMA)_2n‐MI and (PMMA)_4n‐MI were efficiently clicked with the peripheral anthracene functionalized multiarm star polymer, (α‐anthryl functionalized‐polystyrene)_m‐poly(divinyl benzene) ((α‐anthryl‐PS)_m‐polyDVB) through the Diels–Alder reaction resulting in corresponding multiarm star block copolymers: (PMMA)_2n‐(PS)_m‐polyDVB and (PMMA)_4n‐(PS)_m‐polyDVB, respectively. Molecular weights (M_w,TDGPC), hydrodynamic radius (R_h), and intrinsic viscosity (η) of the multiarm star polymers were determined using three‐detection GPC (TD‐GPC). The high efficiency of this methodology to obtain such sterically demanding macromolecular constructs was deduced using ¹H‐NMR and UV–vis spectroscopy. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

An investigation of nonlinear dynamics of a thermal pulse combustor

Nonlinear dynamics of a thermal pulse combustor was investigated using a coupled fourth order lumped combustor model. The effects of optically thin radiation from the combustor gases to the wall are also investigated. The system response changes from steady combustion to extinction through oscillatory combustion as the wall temperature is lowered. The qualitative results suggest a transition to chaos through a period-doubling route prior to extinction. The presence of chaos is also confirmed by quantitative measures like correlation dimension and Lyapunov exponent. The system dynamics is qualitatively similar in presence and absence of radiation. However, inclusion of radiative heat loss leads to extinction at higher temperatures and also increases the predicted range of wall temperatures for which limit cycle behaviour is obtained. A measure for monitoring the proximity of the system to extinction has been developed using the time series data.     

Diameter-dependent coercivity of cobalt nanowires

We show that the coercivity of electrochemically grown cobalt nanowires (NWs) within the pores of a polycarbonate membrane can be changed to a large extent by tuning their diameters. The face centered cubic crystalline structure of the NWs having diameter in the range of 10 to 200 nm could be retained. Smaller diameter wires (below 30 nm) are found to be single crystalline and oriented in the [110] growth direction, but for higher diameter wires the crystallite size became very small. Magnetization measurements with an applied field parallel to the axis of the NWs show that the nature of the M–H loop changes from square to linear as the diameter of the NWs increases. The coercivity was found to be 1700 Oe and 480 Oe at 5 K (1000 Oe and 250 Oe at 300 K) for 10 nm and 100 nm wires, respectively. The observed changes in the nature of the M–H loop and in coercivity could be explained following the Stoner–Wohlfarth model and using the fact that the domain size reduces as the diameter of the wires increases.     

Stabilizing N-tosyl-2-lithioindoles with bis(N,N′-dimethylaminoethyl) ether—a non-cryogenic procedure for lithiation of N-tosylindoles and subsequent addition to ketones

A practical procedure suitable for large scale lithiation of N-tosylindoles and subsequent addition to ketones is described. Bis(N,N′-dimethylaminoethyl) ether was found to stabilize 2-lithio-N-tosylindole 1A at −25 °C [The temperatures cited are internal temperatures unless otherwise stated]. Addition of this reagent allows the lithiation of N-tosyl indoles and subsequent addition to ketones to operate at −25 °C, a temperature suitable for large scale reactions.     

Force Constants and Mean Amplitudes of Vibration of the Thiazyl Halides Cisn and BrSN

The force constants have been calculated for thiazylnalides CISN and BrSN employing general valence force field and Urey-Dradley force field. The computed results show some interesting features. The mean amplitudes of vibration have also been calculated at temperatures, O°K, 298.15°K and 500°K. These results will be helpful for the interpretation of the electron diffraction data whenever available.     

Liquid chromatography/electrospray ionization tandem mass spectrometry validated method for the simultaneous quantification of sibutramine and its primary and secondary amine metabolites in human plasma and its application to a bioequivalence study

A high-throughput and sensitive bioanalytical method using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) has been developed for the estimation of sibutramine and its two metabolites (M1 and M2). The extraction of sibutramine, its metabolites and imipramine (internal standard (IS)) from the plasma involved treatment with phosphoric acid followed by solid-phase extraction (SPE) using a hydrophilic-lipophilic balanced HLB cartridge. The SPE eluate without drying and reconstitution was analyzed by LC/MS/MS, equipped with a with turbo ion spray (TIS) source, operating in the positive and multiple reaction monitoring (MRM) acquisition mode. Sample preparation by this method yielded extremely clean extracts with quantitative and consistent mean recoveries; 95.12% for sibutramine, 92.74% for M1, 95.97% for M2 and 96.60% for the IS. The total chromatographic run time was 3.0 min with retention times of 2.51, 2.13, 2.09 min for sibutramine, M1, M2 and imipramine, respectively. The developed method was validated in human plasma matrix, with a sensitivity of 0.1 ng/mL (coefficient of variance (CV), 2.07%) for sibutramine, 0.1 ng/mL (CV, 3.59%) for M1 and 0.2 ng/mL (CV, 4.93%) for M2. Validation of the method for its accuracy, precision, recovery, matrix effect and stability was carried out especially with regard to real subject sample analysis. The response was linear over the dynamic range 0.1 to 8.0 ng/mL for sibutramine and M1, and 0.2 to 16.0 ng/mL for M2 with correlation coefficients of r > or = 0.9959 (sibutramine), 0.9935 (M1) and 0.9943 (M2). The method was successfully applied for bioequivalence studies in 40 human subjects with 15 mg capsule formulations.     

Perpendicular magnetocrystalline anisotropy in tetragonally distorted Fe-Co alloys

We report on the experimental realization of tetragonal Fe-Co alloys as a constituent of Fe0.36Co0.64/Pt superlattices with huge perpendicular magnetocrystalline anisotropy energy, reaching 210 microeV/atom, and a saturation magnetization of 2.5 microB/atom at 40 K, in qualitative agreement with theoretical predictions. At room temperature the corresponding values and are achieved. This suggests that Fe-Co alloys with carefully chosen combinations of composition and distortion are good candidates for high-density perpendicular storage materials.