Validated liquid chromatography–tandem mass spectrometry method for simultaneous quantitation of bendamustine and copanlisib in mouse plasma: Application to a pharmacokinetic study in mice

In this study, we report the development and validation of an LC–tandem mass spectrometry method for the simultaneous quantitation of bendamustine and copanlisib in mouse plasma as per the US FDA regulatory guidelines. The sample processing involves extraction of bendamustine and copanlisib along with internal standard (IS; warfarin) from 50 μL mouse plasma using a liquid–liquid extraction method. The chromatographic separation of bendamustine, copanlisib and the IS was achieved on an Atlantis dC₁₈ column using an isocratic mobile phase (5 mM ammonium acetate:methanol, 20:80 v/v). Bendamustine, copanlisib and the IS eluted at 0.88, 1.39 and 0.74 min, respectively, with a total run time of 2.5 min. The calibration curve ranged from 3.99–2996 and 4.33–3248 ng/mL for bendamustine and copanlisib, respectively. Inter- and intra-day precision and accuracy, stability in processed samples and upon storage, dilution integrity and incurred sample reanalysis were investigated for both the analytes. The intra- and inter-day precisions were in the ranges of 2.01%–5.05% and 2.74%–6.13% and 1.98%–7.64 and 8.62%–9.04% for bendamustine and copanlisib, respectively. Stability studies showed that both analytes were stable on bench top for 6 h, in auto-sampler for 24 and at −80°C for 30 days. The validated method was successfully applied to a pharmacokinetic study in mice.     

Implementation of the virtual element method for coupled thermo-elasticity in Abaqus

Numerical Algorithms - In this paper, we employ the virtual element method for the numerical solution of linear thermo-elastic problems in two dimensions. The framework is implemented within the...     

Quantitative analysis of enasidenib in dried blood spots of mouse blood using an increased‐sensitivity LC–MS/MS method: Application to a pharmacokinetic study

A simple, sensitive and rapid assay method has been developed and validated as per regulatory guidelines for the estimation of enasidenib on mouse dried blood spots (DBS) using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive‐ion mode. The method employs liquid extraction of enasidenib from DBS disks of mouse whole blood followed by chromatographic separation using 0.2% formic acid–acetonitrile (25:75, v/v) at a flow rate of 1.0 mL/min on an Atlantis dC₁₈ column with a total run time of 2.0 min. The MS/MS ion transitions monitored were m/z 474.0 → 267.1 for enasidenib and m/z 309.2 → 251.3 for the internal standard (warfarin). The assay was linear in the range of 1.01 – 3044 ng/mL. The within‐run and between‐run precisions were in the range of 3.18 – 9.06 and 4.66 – 8.69%, respectively. Stability studies showed that enasidenib was stable on DBS cards for 1 month. This novel method has been applied to analyze the DBS samples of enasidenib obtained from a pharmacokinetic study in mice.     

Separation of uranium from solid (U,Pu, Ag) oxide analytical waste: effect of batch size and nitric acid molarity

This work presents the investigation of some commercially available and commonly used Si₃N₄ foils prepared with LPCVD technique. The density and the stoichiometry of these films were determined by Rutherford backscattering spectroscopy and profilometry, while the study of impurities was achieved with particle induced X-ray emission method. It was found that the density of the studied Si₃N₄ films is significantly less (~2.71 g cm^?3), while the stoichiometry is close to the values of the bulk material. The results were verified by measuring the ion energy loss through the films by scanning transmission ion microscopy.     

Gibbs Sampling with Diffuse Proper Priors: A Valid Approach to Data-Driven Inference?

Abstract

This article demonstrates by example that the use of the Gibbs sampler with diffuse proper priors can lead to inaccurate posterior estimates. Our results show that such inaccuracies are not merely limited to small sample settings.     

A generalization of set-valued Prešić–Reich type contractions in ultrametric spaces with applications

In this paper, we study the existence and uniqueness of coincidence and common fixed point of a set-valued and a single-valued mapping satisfying generalized set-valued Pre?i?–Reich type contractive condition in ultrametric spaces without the property of completeness. As an application, the well-posedness of a common fixed point problem is proved. An example is given to illustrate our results. Our results generalize and extend the results of Pre?i?–Reich in the context of ultrametric spaces.     

Synthesis and Characterization of Related Compounds of Aripiprazole,an Antipsychotic Drug Substance

Three related compounds of aripiprazole were identified during the synthesis. These related compounds were synthesized and characterized by their respective spectral data.     

Stuffed Tridymite Structures: Synthesis,Structure, Second Harmonic Generation,Optical, and Multiferroic Properties

The stuffed tridymite structure Ba(Zn/Co)_1−xSi_1−xM_2xO₄ (M=Al³⁺ and Fe³⁺) is explored for the possible multiferroic behavior and to develop new inorganic colored materials. The compounds were synthesized by employing conventional solid-state chemistry methods in the temperature range 1100–1175 °C for 24 h. The powder X-ray diffraction (PXRD) and Rietveld refinement studies indicate that the compounds stabilize in the P63 space group (no. 173). The refinement results were also rationalized by employing Raman spectroscopic studies. The compounds were found to be second harmonic generation (SHG) active and show weak ferroelectric behavior. The co-substitution of Co²⁺ and Fe³⁺ in the structure gives rise to a weak ferromagnetic behavior to the compound, BaCo_0.75Si_0.75Fe_0.5O₄, making it a multiferroic material. The optical studies on the prepared compounds exhibited blue color (Co²⁺ in T_d geometry), purple color (Ni²⁺ in T_d geometry), and simultaneous substitution of Co²⁺ and Fe³⁺ gives rise to blue-green color owing to metal-to-metal charge transfer (MMCT) effect.     

Synthesis,structure, photophysical,and electrochemical properties of donor–acceptor ferrocenyl derivatives

A series of donor–acceptor compounds 2–6 have been synthesized, via Knoevenagel condensation reaction (using conventional method, as well as microwave method). The ferrocene unit acts as a donor, conjugated phenyl–acetylene linker act as a π-electron relay unit, and malononitrile, cyanoacetic acid, and indanone groups act as acceptor. The electronic absorption spectra displayed a broad intramolecular charge transfer (CT) band in the visible region (450–650 nm). The electrochemical studies suggest considerable donor–acceptor interaction. The single crystal X-ray structure of 2, and 3 are reported, the structure reveals that 2 is nearly planar compared to 3. The supramolecular structure of 2 exhibits intramolecular C–H–π, and C–H–N interaction, which leads to formation of 2D network, whereas compound 3 shows head to tail dimer formation through C–H–π, and π–π interaction.