Nevirapine quantification in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry. Application to bioequivalence study

A rapid, sensitive and specific method to quantify nevirapine in human plasma using dibenzepine as the internal standard (IS) was developed and validated. The method employed a liquid-liquid extraction. The analyte and the IS were chromatographed on a C(18) analytical column, (150 x 4.6 mm i.d. 4 microm) and analyzed by tandem mass spectrometry in the multiple reaction monitoring mode. The method had a chromatographic run time of 5.0 min and a linear calibration curve over the range 10-5000 ng ml(-1) (r(2) > 0.9970). The between-run precision, based on the relative standard deviation for replicate quality controls was 1.3% (30 ng ml(-1)), 2.8% (300 ng ml(-1)) and 3.6% (3000 ng ml(-1)). The between-run accuracy was 4.0, 7.0 and 6.2% for the above-mentioned concentrations, respectively. This method was employed in a bioequivalence study of two nevirapine tablet formulations (Nevirapina from Far-Manguinhos, Brazil, as a test formulation, and Viramune from Boehringer Ingelheim do Brasil Química e Farmacêutica, as a reference formulation) in 25 healthy volunteers of both sexes who received a single 200 mg dose of each formulation. The study was conducted using an open, randomized, two-period crossover design with a 3 week washout interval. The 90% confidence interval (CI) of the individual ratio geometric mean for Nevirapina/Viramune was 96.4-104.5% for AUC((0-last)), 91.4-105.1% for AUC((0-infinity)) and 95.3-111.6% for C(max) (AUC = area under the curve; C(max) = peak plasma concentration). Since both 90% CI for AUC((0-last)) and AUC((0-infinity)) and C(max) were included in the 80-125% interval proposed by the US Food and Drug Administration, Nevirapina was considered bioequivalent to Viramune according to both the rate and extent of absorption.     

Inclusion complexes of Schiff bases as phytogrowth inhibitors

This article details the preparation, characterization and phytotoxic evaluation of several Schiff base inclusion complexes obtained from β-cyclodextrin and p-sulfonic acid calix[6]arene. The inclusion complexes (1:1 molar ratio) were prepared by mixing a 5 mmol L^?1 aqueous solution (containing 1 % DMSO) of Schiff bases (guests) with aqueous solution (containing 1 % DMSO) of 5 mmol L^?1 of β-cyclodextrin or p-sulfonic acid calix[6]arene (hosts). The host–guest systems were characterized via a series of NMR experiments. The ability of the complexes to interfere with the radicle elongation of Sorghum bicolor (dicotyledonous species) and Cucumis sativus (monocotyledonous species) was evaluated. After 48 h, the inclusion complexes inhibited the radicle elongation of both species from 11 to 56 %. The formation of inclusion complexes was also investigated theoretically by molecular dynamics simulations in aqueous solution through implicit approach. Based on the experimental observation, the phytotoxic activity evaluated can be attributed to the formation of host–guest systems. This was supported by the theoretical findings based on stable interaction energy analyses for all the studied supramolecular systems.     

Detection of Plasmon Coupling between Silver Nanowires Based on Hyperspectral Darkfield and SERS Imaging and Supported by DDA Theoretical Calculations

We report the unprecedented observation of plasmon coupling between silver nanowires, showing how the surface‐enhanced Raman scattering depends upon this interaction and how the spectrum can be shaped by the hot spot. Such observations were accomplished by Raman spectroscopy mapping of silver nanowires modified with rhodamine. The local spectra on the hot spots were measured by darkfield hyperspectral microscopy, a powerful but uncommonly used technique that is capable of determining the location, structure, and spectra of the hot spots. The result obtained by the simulation of two parallel nanowires based on the discrete dipole approximation (DDA) method was in excellent agreement with the results obtained experimentally.     

Ab initio calculations on low-energy conformers of alpha-cyclodextrin

In this article we carried out a comprehensive investigation of true minima on the potential energy surface (PES) for the alpha-cyclodextrin molecule using ab initio Hartree-Fock (HF) and density functional theory (DFT) quantum chemical methods, employing basis sets ranging from 6-31 G(d,p) to 6-311++G(2d,2p) triple-zeta quality. Thermodynamic quantities and the solvent effect were evaluated at the DFT level of theory. We believe that the most relevant conformers present on the multidimensional PES were sampled in our work, using an adequate treatment of electron correlation effects to describe the intramolecular hydrogen bonds that are present in cyclodextrin species. We present new structures not reported so far and discuss, in detail, the relevance of the DFT gas-phase equilibrium structures for the experimental and theoretical studies involving cyclodextrins and corresponding inclusion complexes, in the condensed phase. In addition, among the various true minimum energy structures located on the DFT PES, the preferred structures in the gas phase and aqueous media, needed to be used as representative minima on the PES in further studies involving the interaction of alpha-cyclodextrin with other species, were unambiguously identified.     

Degenerate two-photon absorption spectra in azoaromatic compounds.

A systematic study of the degenerate two-photon absorption (2PA) spectra of seven azoaromatic compounds in dimethyl sulfoxide solution is reported, which employed the Z-scan technique with femtosecond laser pulses from the bottom of the azo compound absorption bands up to 1100 nm. The 2PA peaks for pseudostilbene-type azo compounds (Disperse Orange (DO) 3, Disperse Red (DR) 13, DR1, DR19, and DR19-Cl) were observed at twice the peak wavelength of the linear absorption. However, such peaks were not observed for other azo compounds (PAMINO and DIAMINO) because of the symmetry of these molecules. A resonance enhancement of the 2PA cross-section was observed for all compounds. The 2PA peak and the nonlinear resonance enhancement behavior could be adjusted with a model based on perturbation theory. Such knowledge can be a guideline to the understanding of the 2PA process in azoaromatic compounds.     

Fluorescent PMMA/MEH‐PPV electrospun nanofibers: Investigation of morphology,solvent, and surfactant effect

Electrospinning is a powerful technique to produce nanofibers of tunable diameter and morphology for medicine and biotechnological applications. By doping electrospun nanofibers with inorganic and organic compounds, new functionalities can be provided for technological applications. Herein, we report a study on the morphology and optical properties of electrospun nanofibers based on the conjugated polymer poly[2‐methoxy‐5‐(2‐ethylhexyloxy)‐1,4‐phenylenevinylene] (MEH‐PPV) and poly(methylmethacrylate) (PMMA). Initially, we investigate the influence of the solvent, surfactant, and the polymer concentration on electrospinning of PMMA. After determining the best conditions, 0.1% MEH‐PPV was added to obtain fluorescent nanofibers. The optical characterizations display the successful impregnation of MEH‐PPV into the PMMA fibers without phase separation and the preservation of fluorescent property after fiber electrospinning. The obtained results show the ability of the electrospinning approach to obtain fluorescent PMMA/MEH‐PPV nanofibers with potential for optical devices applications. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014 , 52, 1388–1394     

New succinyl‐spaced pyrazoles: Regioselective synthesis of 1,4‐bis[5‐(trichloromethyl)‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones

The facile and convenient access by a conventional procedure in ethanol as solvent to a new series of succinyl‐spaced pyrazoles including 1,4‐bis[5‐(trichloromethyl)‐5‐hydroxy‐4,5‐dihydro‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones (64–82%) and the respective dehydrated derivatives as 1,4‐bis[5‐(trichloromethyl)‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones in 57–82% yields, from the regioselective cyclocondensation reactions of 4‐substituted 4‐methoxy‐1,1,1‐trichloroalk‐3‐en‐2‐ones with succinic acid dihydrazide, where the 4‐substituents are Me, Ph, 4‐FC₆H₄, 4‐ClC₆H₄, 4‐NO₂C₆H₄, 2‐furyl, and 2‐thienyl, is reported. J. Heterocyclic Chem., 2011.