UPLC‐MS/MS assay for the simultaneous quantification of carvedilol and its active metabolite 4′‐hydroxyphenyl carvedilol in human plasma to support a bioequivalence study in healthy volunteers

An ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS) method has been developed for the simultaneous determination of carvedilol and its pharmacologically active metabolite 4′‐hydroxyphenyl carvedilol in human plasma using their deuterated internal standards (IS). Samples were prepared by solid‐phase extraction using 100 μL human plasma. Chromatographic separation of analytes was achieved on UPLC C18 (50 × 2.1 mm, 1.7 µm) column using acetonitrile‐4.0 mm ammonium formate, pH 3.0 adjusted with 0.1% formic acid (78:22, v/v) as the mobile phase. The multiple reaction monitoring transitions for both the analytes and IS were monitored in the positive electrospray ionization mode. The method was validated over a concentration range of 0.05–50 ng/mL for carvedilol and 0.01‐10 ng/mL for 4′‐hydroxyphenyl carvedilol. Intra‐ and inter‐batch precision (% CV) and accuracy for the analytes varied from 0.74 to 3.88 and 96.4 to 103.3% respectively. Matrix effect was assessed by post‐column analyte infusion and by calculation of precision values (coefficient of variation) in the measurement of the slope of calibration curves from eight plasma batches. The assay recovery was within 94–99% for both the analytes and IS. The method was successfully applied to support a bioequivalence study of 12.5 mg carvedilol tablets in 34 healthy subjects. Copyright © 2013 John Wiley & Sons, Ltd.     

Dendron–polymer conjugates via the diels–alder “click” reaction of novel anthracene‐based dendrons

Diblock and triblock dendron–polymer conjugates containing biodegradable polyester dendron blocks and polyethylene glycol (PEG) polymer were synthesized using the Diels–Alder “click” cycloaddition reaction. PEG polymers with furan‐protected maleimide functionality were synthesized and reacted with biodegradable polyester dendrons containing an anthracene moiety at their focal point. First through third generations of biodegradable polyester dendrons containing an anthracene unit at their focal point were synthesized using a divergent strategy. Efficient conjugation of the dendrons to polymers was demonstrated using ¹HNMR and size exclusion chromatography. This modular approach provides an easy access to the design of multivalent PEG conjugates. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3191–3201     

Optimization of chromatography to overcome matrix effect for reliable estimation of four small molecular drugs from biological fluids using LC–MS/MS

The article describes a systematic study to overcome the matrix effect during chromatographic analysis of gemfibrozil, rivastigmine, telmisartan and tacrolimus from biological fluids using LC–ESI–MS/MS. All four methods were thoroughly developed by the appropriate choice of analytical column, elution mode and pH of mobile phase for improved chromatography and overall method performance. Matrix effect was assessed by post-column analyte infusion, slope of calibration line approach and post-extraction spiking. The best chromatographic conditions established were: Acquity BEH C₁₈ (50 × 2.1 mm, 1.7 μm) column with 5.0 mm ammonium acetate, pH 6.0–methanol as the mobile phase under gradient program for gemfibrozil; Luna CN (50 × 2.0 mm, 3 μm) column with a mobile phase consisting of acetonitrile–10 mm ammonium acetate, pH 7.0 (90:10, v/v) for rivastigmine; Inertsustain C₁₈ (100 × 2.0 mm, 5 μm) column using methanol–2.0 mm ammonium formate, pH 5.5 (80: 20, v/v) as the mobile phase for isocratic elution of telmisartan; and Acquity BEH C₁₈ (50 × 2.1 mm, 1.7 μm) with methanol–10 mm ammonium acetate, pH 6.0 (95:5, v/v) as mobile phase for tacrolimus. The methods were thoroughly validated as per European Medicines Agency and US Food and Drug Administration guidance and were successfully applied for pharmacokinetic studies in healthy subjects.     

Ab initio calculations of B<Subscript>2</Subscript> type RHg (R = Ce,Pr, Eu and Gd) intermetallic compounds

Spin polarized ab initio calculations have been carried out to study the structural, electronic, elastic and thermal properties of RHg (R = Ce, Pr, Eu and Gd) intermetallic compounds in B₂ structure. The calculations have been performed by using both generalized gradient approximation (GGA) and local spin density approximation (LSDA). The calculated value of lattice constant (a ₀) for these compounds with GGA is in better agreement with the experimental data than those with LSDA. Bulk modulus (B), first-order pressure derivative of bulk modulus and magnetic moment (μ _B ) are also presented. The energy band structure and electron density of states show the occupancy of 4f states for light as well as heavy rare earth atom. The elastic constants are predicted from which all the related mechanical properties like Poisson’s ratio (σ), Young’s modulus (E), shear modulus (G _H ) and anisotropy factor (A) are calculated. The ductility or brittleness of these compounds is predicted from Pugh’s rule (B/G _H ) and Cauchy pressure (C ₁₂ ? C ₄₄). The Debye temperature (θ _D ) is estimated from the average sound velocity, which have not been calculated and measured yet.     

Valence-band electronic structure of iron phthalocyanine: an experimental and theoretical photoelectron spectroscopy study

The electronic structure of iron phthalocyanine (FePc) in the valence region was examined within a joint theoretical-experimental collaboration. Particular emphasis was placed on the determination of the energy position of the Fe 3d levels in proximity of the highest occupied molecular orbital (HOMO). Photoelectron spectroscopy (PES) measurements were performed on FePc in gas phase at several photon energies in the interval between 21 and 150 eV. Significant variations of the relative intensities were observed, indicating a different elemental and atomic orbital composition of the highest lying spectral features. The electronic structure of a single FePc molecule was first computed by quantum chemical calculations by means of density functional theory (DFT). The hybrid Becke 3-parameter, Lee, Yang and Parr (B3LYP) functional and the semilocal 1996 functional of Perdew, Burke and Ernzerhof (PBE) of the generalized gradient approximation (GGA-)type, exchange-correlation functionals were used. The DFT/B3LYP calculations find that the HOMO is a doubly occupied π-type orbital formed by the carbon 2p electrons, and the HOMO-1 is a mixing of carbon 2p and iron 3d electrons. In contrast, the DFT/PBE calculations find an iron 3d contribution in the HOMO. The experimental photoelectron spectra of the valence band taken at different energies were simulated by means of the Gelius model, taking into account the atomic subshell photoionization cross sections. Moreover, calculations of the electronic structure of FePc using the GGA+U method were performed, where the strong correlations of the Fe 3d electronic states were incorporated through the Hubbard model. Through a comparison with our quantum chemical calculations we find that the best agreement with the experimental results is obtained for a U(eff) value of 5 eV.     

Development of Layered Multiscale Porous Thin Films by Tuning Deposition Time and Molecular Weight of Polyelectrolytes

This work focuses on the design of porous polymeric films with nano‐ and micro‐sized pores existing in distinct zones. The porous thin films are fabricated by the post‐treatment of layer‐by‐layer assembled poly(allylamine hydrochloride) (PAH)/poly(acrylic acid) (PAA) multilayers. In order to improve the processing efficiency, the deposition time is shortened to ≈10 s. It is found that fine porous structures can be created even by significantly reducing the processing time. The effect of using polyelectrolytes with widely different molecular weights is also studied. The pore size is increased by using high molecular weight PAH, while high molecular weight PAA minimizes the pore size to nanometer scale. Having gained a precise control over the pore size, layered multiscale porous thin films are further built up with either a microsized porous zone on top of a nanosized porous zone or vice versa.

     

Novel effects of localization due to intrinsic disorder in manganites

We discuss the effects of a novel ‘intrinsic’ disorder in hole-doped rare-earth manganites. Using effective field theory as well as direct numerical simulations, we show that this disorder can have dramatic effects in terms of the transition from ferromagnetic insulator to ferromagnetic metal upon hole-doping, including an Anderson localized regime where variable range hopping may be observed.     

Diffusing wave spectroscopy of dense colloids: Liquid,crystal and glassy states

Using intensity autocorrelation of multiply scattered light, we show that the increase in interparticle interaction in dense, binary colloidal fluid mixtures of particle diameters 0.115μm and 0.089μm results in freezing into a crystalline phase at volume fractionφ of 0.1 and into a glassy state atφ=0.2. The functional form of the field autocorrelation functiong ⁽¹⁾(t) for the binary fluid phase is fitted to exp[−γ(6k ₀ ² D _eff t)^1/2] wherek ₀ is the magnitude of the incident light wavevector andγ is a parameter inversely proportional to the photon transport mean free pathl*. TheD _eff is thel* weighted average of the individual diffusion coefficients of the pure species. Thel* used in calculatingD _eff was computed using the Mie theory. In the solid (crystal or glass) phase, theg ⁽¹⁾(t) is fitted (only with a moderate success) to exp[−γ(6k ₀ ² W(t))^1/2] where the mean-squared displacementW(t) is evaluated for a harmonically bound overdamped Brownian oscillator. It is found that the fitted parameterγ for both the binary and monodisperse suspensions decreases significantly with the increase of interparticle interactions. This has been justified by showing that the calculated values ofl* in a monodisperse suspension using Mie theory increase very significantly with the interactions incorporated inl* via the static structure factor.     

X-ray scattering studies of surfaces and interfaces

Here we shall briefly review the basics and some applications of x-ray specular reflectivity and diffuse scattering techniques. These x-ray scattering techniques are uniquely suited to study of the structure of surfaces and interfaces at atomic resolutions as they are nondestructive and can probe even interfaces which are buried. The study of structure of surfaces and interfaces is not only required in understanding physics in reduced dimensions but is also essential in developing technologically important materials.     

Two phonon density of states of partially disordered crystal NH4I

Two phonon density of states of NH₄ have been computed with the help of deformation dipole model at room temperature. The results have been compared with the available experimental Raman Spectrum and peak position. It has been shown that in addition to single phonon process which is dominant, the two-phonon density of states also contribute to the Raman Intensity in a partially disordered crystal.