Development and validation of a LC-MS/MS method for d-cycloserine determination in human plasma for bioequivalence study

A reliable and high throughput high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated for determining levels of the antitubercular drug-d -cycloserine in human plasma. Plasma samples analyte with an internal standard (IS) (niacin) were prepared by solid-phase extraction using Waters Oasis MCX cartridges. The chromatographic separation was performed using the HILIC mode on a YMC-Pack SIL-06 column (150?×?4.6 mm; 3 μm) under isocratic conditions. The run time of analysis was 5 min. The mobile phase consisted of methanol, propanol-2 and 0.075 % trifluoroacetic acid (66.5:28.5:5, v/v/v). Protonated ions formed by turbo ion spray in positive mode were used to detect the analyte and the IS. MS/MS detection was used to monitor the fragmentation of 103–75?m/z for cycloserine and 124 to 80?m/z for niacin (IS) on an API 4000 (AB Sciex) triple quadrupole mass spectrometer. A linear dynamic range of 0.3–30 μg/mL was established for cycloserine using 0.2 mL human plasma and a 1 μL injection volume. The mean relative recovery of cycloserine and niacin were 77.2 and 82.4 %, respectively. The procedure of sample preparation was consistent and reproducible (precision, 0.8–3.4 %; accuracy, 93.8–104.9 %). The method was validated in accordance with requirements of the European Medicines Agency and successfully applied to a bioequivalence study of 250 mg tablet formulations in 23 healthy human subjects.     

Determination of rhenium and osmium complexes by surface-assisted laser desorption/ionization coupled to Orbitrap mass analyzer

A surface-assisted laser desorption/ionization (SALDI) source is coupled to the Orbitrap mass analyzer; the instrumental approach is tested for the analysis of rhenium (Re) and osmium (Os) complexes with 8-mercaptoquinoline. Silicon (Si) material obtained by laser treatment of monocrystalline Si is used as SALDI substrate. All studied complexes are detected as radical cations, with no protonated molecules. The comparison of SALDI, matrix-assisted laser desorption/ionization (MALDI), and direct laser desorption/ionization (LDI) on metal plates in the same instrumental setup demonstrated that the detection of the studied complexes using SALDI provides the highest sensitivity. The ability to analyze samples rapidly, high purity of spectra, and good analytical parameters make SALDI coupled to the Orbitrap mass analyzer a potentially powerful tool for the detection of Re and Os complexes and related organic, UV-absorbing compounds.

Enumeration of non-labile oxygen atoms in dissolved organic matter by use of 16O/18O exchange and Fourier transform ion-cyclotron resonance mass spectrometry

We report a simple approach for enumeration of non-labile oxygen atoms in individual molecules of dissolved organic matter (DOM), using acid-catalyzed ¹⁶O/¹⁸O exchange and ultrahigh-resolution Fourier-transform ion-cyclotron-resonance mass spectrometry (FTICR-MS). We found that by dissolving DOM in H₂ ¹⁸O at 95 °C for 20 days it is possible to replace all oxygen atoms of DOM molecules (excluding oxygen from ether groups) with ¹⁸O. The number of exchanges in each molecule can be determined using high-resolution FTICR. Using the proposed method we identified the number of non-labile oxygen atoms in 231 molecules composing DOM. Also, using a previously developed hydrogen–deuterium (H/D)-exchange approach we identified the number of labile hydrogen atoms in 450 individual molecular formulas. In addition, we observed that several backbone hydrogen atoms can be exchanged for deuterium under acidic conditions. The method can be used for structural and chemical characterization of individual DOM molecules, comparing different DOM samples, and investigation of biological pathways of DOM in the environment.     

Injectable,Interconnected, High‐Porosity Macroporous Biocompatible Gelatin Scaffolds Made by Surfactant‐Free Emulsion Templating

High‐porosity interconnected, thermoresponsive macroporous hydrogels are prepared from oil‐in‐water high internal phase emulsions (HIPEs) stabilized by gelatin‐graft‐poly(N‐isopropylacrylamide). PolyHIPEs are obtained by gelling HIPEs utilizing the thermoresponsiveness of the copolymer components. PolyHIPEs properties can be controlled by varying the aqueous phase composition, internal phase volume ratio, and gelation temperature. PolyHIPEs respond to temperature changes experienced during cell seeding, allowing fibroblasts to spread, proliferate, and penetrate into the scaffold. Encapsulated cells survive ejection of cell‐laden hydrogels through a hypodermic needle. This system provides a new strategy for the fabrication of safe injectable biocompatible tissue engineering scaffolds.

     

Enhancement of single‑photon emission from nitrogen‑vacancy centers with TiN/(Al,Sc)N hyperbolic metamaterial

The broadband enhancement of single‑photon emission from nitrogen‐vacancy centers in nanodiamonds coupled to a planar multilayer metamaterial with hyperbolic dispersion is studied experimentally. The metamaterial is fabricated as an epitaxial metal/dielectric superlattice consisting of CMOS‐compatible ceramics: titanium nitride (TiN) and aluminum scandium nitride (Al_xSc_1‐xN). It is demonstrated that employing the metamaterial results in significant enhancement of collected single‑photon emission and reduction of the excited‐state lifetime. Our results could have an impact on future CMOS‐compatible integrated quantum sources.

     

Energy-momentum conserving discretization of mixed shell elements for large deformation problems

In the present paper we consider structure-preserving integration methods in the context of mixed finite elements. The used low-order mixed finite elements typically exhibit improved coarse mesh accuracy. On the other hand energy-momentum (EM) consistent time-stepping schemes have been developed in the realm of nonlinear structural dynamics to enhance the numerical stability properties. EM schemes typically exhibit superior robustness and thus offer the possibility to use large time steps while still producing physically meaningful results. Accordingly, combining mixed finite element discretizations in space with EM consistent discretizations in time shows great promise for the design of numerical methods with superior coarse mesh accuracy in space and time. Starting with a general Hu-Washizu-type variational formulation we develop a second-order accurate structure-preserving integration scheme. The present approach is applicable to a large number of mixed finite element formulations. As sample application we deal with a specific mixed shell element. Numerical examples dealing with large deformations will show the improved coarse mesh accuracy in space and time of the advocated approach. (© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

A stress-velocity least-squares mixed finite element formulation for incompressible elastodynamics

In the framework of solving elastodynamic problems using a least-squares mixed finite element method (LSFEM) the implementation of a stress-velocity formulation for small strains is introduced and discussed in the present contribution. The element formulation is based on a first-order div – grad system, with the balance equation of momentum and the constitutive law as the governing equations. Application of the L₂-norm to the two residuals leads to a functional depending on stresses and velocities. Different time discretization schemes are considered, a scalar weighting is introduced and chosen in dependency of the different time discretization methods. In a numerical example the influence of the time integration method, the chosen time step width and the related weighing factor are investigated for a two-dimensional problem. (© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Weighted overconstrained least-squares mixed finite elements for hyperelasticity

The present contribution aims to improve the least-squares finite element method (LSFEM) with respect to the approximation quality in hyperelasticity. We consider a geometrically nonlinear elastic setup and here especially bending dominated problems. Compared with other variational approaches as for example the Galerkin method, the main drawback of least-squares formulations is the unsatisfying approximation quality in terms of accuracy and robustness of especially lower-order elements, see e.g. SCHWARZ ET AL. [1]. In order to circumvent these problems, we introduce an overconstrained first-order stress-displacement system with suited weights. For the interpolation of the unknowns standard polynomials for the displacements and vector-valued Raviart-Thomas functions for the approximation of the stresses are used. Finally, a numerical example is presented in order to show the improvement of performance and accuracy. (© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Comparison of a mixed least-squares formulation using different approximation spaces

The main goal of the present work is the comparison of the performance of a least-squares mixed finite element formulation where the solution variables (displacements and stresses) are interpolated using different approximation spaces. Basis for the formulation is a weak form resulting from the minimization of a least-squares functional, compare e.g. [1]. As suitable functions for standard interpolation polynomials of Lagrangian type are chosen. For the conforming discretization of the Sobolev space vector-valued Raviart-Thomas interpolation functions, see also [2], are used. The resulting elements are named as P_mP_k and RT_mP_k. Here m (stresses) and k (displacements) denote the approximation order of the particular interpolation function. For the comparison we consider a two-dimensional cantilever beam under plain strain conditions and small strain assumptions. (© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)