Quantitative determination of enzalutamide,an anti‐prostate cancer drug,in rat plasma using liquid chromatography–tandem mass spectrometry,and its application to a pharmacokinetic study

This report details a method using liquid chromatography–tandem mass spectrometry (LC‐MS/MS) that allows one to determine the concentration of an atypical anticancer drug, enzalutamide, in rat plasma. Specifically, this method involves the addition of an acetonitrile and bicalutamide (internal standard) solution to plasma samples. Following centrifugation of this mixture, an aliquot of the supernatant was directly injected into the LC‐MS/MS system. Separation was achieved using a column packed with octadecylsilica (5 µm, 2.1 × 50 mm) with 10 mM ammonium acetate in acetonitrile as the mobile phase; detection was accomplished using MS/MS by multiple‐reaction monitoring via an electrospray ionization source. This method demonstrated a linear standard curve (r = 0.997) over a concentration range of 0.001–1 µg/mL, as well as an intra‐ and inter‐assay precision of 2.7 and 5.1%, respectively, and an accuracy range from 100.8 to 105.6%. The lower limit of quantification was 1.0 ng/mL in 50 μL of rat plasma sample. We also demonstrated that this analytical method could be successfully applied to the pharmacokinetic study of enzalutamide in rats. Copyright © 2014 John Wiley & Sons, Ltd.     

A Kinetic Study for the Noncatalytic Esterification of Palm Fatty Acid Distillate

In this work, the reaction scheme for the esterification of palm fatty acid distillate performed under the noncatalytic and high‐temperature condition (230–290°C) was investigated with a rigorous mathematical modeling. The esterification reaction was assumed to be the pseudo–homogeneous second‐order reversible reaction, and the mass transfer effectiveness factor (η) was introduced in the modeling framework to systematically and collectively consider both evaporation and reaction, which are simultaneously and competitively occurred in the liquid phase. The nonlinear programming problem was constructed with the objective function consisting of the errors between experimental data and the estimated values from the reaction model. The problem was solved by using the Nelder–Mead simplex algorithm to identify kinetic parameters, reaction rate constants, and mass transfer coefficients. The values of mass transfer coefficients were found to follow the Hertz–Knudsen relation and expressed as a function of reaction temperature. From the reaction rate constants obtained from the proposed kinetic models, the apparent activation energy was estimated to be 43.98 kJ/mol, which is lower than the value obtained from the reaction using heterogeneous catalysts. This low value indicates that reactants and products behave as an acid catalyst at relatively high operating temperature and constant pressure.     

Spectrochemical analysis of powder using 355 nm Nd-YAG laser-induced low-pressure plasma

The applicability of spectrochemical analysis of minute amounts of powder samples was investigated using an ultraviolet Nd-YAG laser (355 nm) and low-pressure ambient air. A large variety of chemical powder samples of different composition were employed in the experiment. These included a mixture of copper(II) sulfate pentahydrate, zinc sulfide, and chromium(III) sulfate n-hydrate powders, baby powder, cosmetic powders, gold films, zinc supplement tablet, and muds and soils from different areas. The powder samples were prepared by pulverizing the original samples to an average size of around 30 μm in order to trap them in the tiny micro holes created on the surface of the quartz subtarget. It was demonstrated that in all cases studied, good quality spectra were obtained with low background, free from undesirable contamination by the subtarget elements and featuring ppm sensitivity. A further measurement revealed a linear calibration curve with zero intercept. These results clearly show the potential application of this technique for practical qualitative and quantitative spectrochemical analysis of powder samples in various fields of study and investigation.     

A facile approach to synthesize uniform hydrogel shells with controllable loading and releasing properties

We present a facile and straightforward method to synthesize uniform poly(vinyl amine) hydrogel shells with excellent loading capability for active materials and controllable responsiveness to applied stimuli, providing tunable releasing properties.     

The kinetics of competing multiple-barrier unimolecular dissociations of o-, m-, and p-chlorotoluene radical cations

The kinetics of competing multiple-barrier unimolecular dissociations of o-, m-, and p-chlorotoluene radical cations to C7H7(+) (benzyl and tropylium) are studied by ab initio/Rice-Ramsperger-Kassel-Marcus (RRKM) calculations. This system presents a very intriguing kinetic example in which the conventional approach assuming a single-barrier or a double-well potential surface with one transition state cannot predict or explain the outcome. The molecular parameters obtained at the SCF level of theory with the DZP basis set are utilized for the evaluation of microcanonical RRKM rate constants with no adjustable parameters. First-principles calculations provide the microscopic details of the reaction kinetics along the two competing multiple-barrier reaction pathways: the rate-energy curves for all elementary steps; temporal variations of the reactants, the reaction intermediates, and the products; and the product yield as a function of energy. The rate constant for each channel is calculated as a function of the internal energy at 0 K. After the thermal correction, the calculated rate-energy curves for the benzyl channel agree well with the photoelectron photoion coincidence data obtained at room temperature for all three isomers. Close agreement between experiments and theory suggests that first-principles calculations taking the full sequence of kinetic steps into account offer a useful kinetic model capable of correctly predicting the outcome of competing multiple-barrier reactions. The slowest process is identified as [1,2] and [1,3] alpha-H migration at the entrance to the tropylium and benzyl channel, respectively. However, the overall rate is determined not by the slowest process, but by the combination of the slowest rate and the net flux toward the product, which is multiplicatively reduced with an increasing number of reaction intermediates. The product yield calculation confirms the benzyl cation as the predominant product. For all isomers, the thermodynamically most stable tropylium ion is produced much less than expected because a large fraction of flux coming into the tropylium channel goes back to the benzyl channel. The benzyl channel is kinetically favored because it involves a lower entrance barrier with fewer rearrangements than the tropylium channel.     

Singular values of some modular functions and their applications to class fields

Since the modular curve has genus zero, we have a field isomorphism where X ₂(z) is a product of Klein forms. We apply it to construct explicit class fields over an imaginary quadratic field K from the modular function j _Δ,25(z):=X ₂(5z). And, for every integer N≥7 we further generate ray class fields K _(N) over K with modulus N just from the two generators X ₂(z) and X ₃(z) of the function field , which are also the product of Klein forms without using torsion points of elliptic curves. J.K. Koo was supported by Korea Research Foundation Grant (KRF-2002-070-C00003).     

Melampolides from the leaves of Smallanthus sonchifolius and their inhibitory activity of lps-induced nitric oxide production

Two new melampolide-type sesquiterpene lactones, 8beta-epoxyangeloyloxy-9alpha-ethoxy-14-oxo-acanthospermolide (1) and 8beta-angeloyloxy-9alpha-ethoxy-14-oxo-acanthospermolide (2), were isolated from the leaves of yacon [Smallanthus sonchifolia (POEPP. et ENDL.) H. Robinson] along with eleven known melampolides, allo-schkuhriolide (3), enhydrin (4), polymatin A (5), fluctuanin (6), 8beta-angeloyloxy-9alpha-acetoxy-14-oxo-acanthospermolide (7), 8beta-angeloyloxy-14-oxo-acanthospermolide (8), 8beta-methacryloyloxymelampolid-14-oic acid methyl ester (9), uvedalin (10), polymatin B (11), 8beta-tigloyloxymelampolid-14-oic acid methyl ester (12), and sonchifolin (13). Their structures were established on the basis of spectroscopic evidence including 1D- and 2D-NMR experiments. All isolates were evaluated for inhibition of LPS-induced nitric oxide production in murine macrophage RAW 264.7 cells.     

Analysis of the spin lattice model for the spin-gapped layered compounds Na(3)Cu(2)SbO(6) and Na(2)Cu(2)TeO(6) on the basis of electronic structure calculations

The spin lattice model for the spin-gapped layered magnetic solids Na3Cu2SbO6 and Na2Cu2TeO6 was examined by evaluating the three spin exchange interactions of their Cu2MO6 (M = Sb, Te) layers in terms of spin dimer analysis based on extended Hückel tight binding calculations and mapping analysis based on first principles density functional theory electronic band structure calculations. For both compounds, our calculations show that the two strongest spin exchange interactions, that is, the Cu-O...O-Cu super-superexchange (J2) and the Cu-O-Cu superexchange (J1) interactions, form alternating chains that interact weakly through the Cu-O-Cu superexchange (J3) interactions. The dominant one of the three spin exchange interactions is J2, and it is antiferromagnetic in agreement with the fact that both of the compounds are spin gapped. For Na3Cu2SbO6 and Na2Cu2TeO6, the superexchange J1 is calculated to be ferromagnetic, hence, leading to the alternating chain model in which antiferromagnetic and ferromagnetic spin exchange interactions alternate. This picture does not agree with the recent experimental analysis, which showed that the temperature-dependent magnetic susceptibilities of both compounds should be described by the alternating chain model in which two antiferromagnetic spin exchange interactions of different strengths alternate.     

Heterometallic integer-spin analogues of S = 9/2 Mn4 cubane single-molecule magnets

A family of distorted heterometallic cubanes, [Mn (III) 3Ni (II)(hmp) 3O(N 3) 3(O 2CR) 3], where O 2CR (-) is benzoate ( 1), 3-phenylpropionate ( 2), 1-adamantanecarboxylate ( 3), or acetate ( 4) and hmp (-) is the anion of 2-pyridinemethanol, was synthesized and structurally as well as magnetically characterized. These complexes have a distorted-cubane core structure similar to that found in the S = 9/2 Mn 4 cubane family of complexes. Complexes 1, 3, and 4 crystallize in rhombohedral, hexagonal, and cubic space groups, respectively, and have C 3 molecular symmetry, while complex 2 crystallizes in the monoclinic space group Cc with local C 1 symmetry. Magnetic susceptibility and magnetization hysteresis measurements and high-frequency electron paramagnetic resonance (HFEPR) spectroscopy established that complexes 1-4 have S = 5 spin ground states with axial zero-field splitting (ZFS) parameters ( D) ranging from -0.20 to -0.33 cm (-1). Magnetization versus direct-current field sweeps below 1.1 K revealed hysteresis loops with magnetization relaxation, definitely indicating that complexes 1-4 are single-molecule magnets that exhibit quantum tunneling of magnetization (QTM) through an anisotropy barrier. Complex 2 exhibits the smallest coercive field and fastest magnetization tunneling rate, suggesting a significant rhombic ZFS parameter ( E), as expected from the low C 1 symmetry. This was confirmed by HFEPR spectroscopy studies on single crystals that gave the following parameter values for complex 2: gz = 1.98, gx = gy = 1.95, D = -0.17 cm (-1), B 4 (0) = -6.68 x 10 (-5) cm (-1), E = 6.68 x 10 (-3) cm (-1), and B 4 (2) = -1.00 x 10 (-4) cm (-1). Single-crystal HFEPR data for complex 1 gave g z = 2.02, gx = gy = 1.95, D = -0.23 cm (-1), and B 4 (0) = -5.68 x 10 (-5) cm (-1), in keeping with the C 3 site symmetry of this Mn 3Ni complex. The combined results highlight the importance of spin-parity effects and molecular symmetry, which determine the QTM rates.