A gadolinium-based magnetic ionic liquid for supramolecular dispersive liquid–liquid microextraction followed by HPLC/UV for the determination of favipiravir in human plasma

Favipiravir is a potential antiviral medication that has been recently licensed for Covid-19 treatment. In this work, a gadolinium-based magnetic ionic liquid was prepared and used as an extractant in dispersive liquid–liquid microextraction (DLLME) of favipiravir in human plasma. The high enriching ability of DLLME allowed the determination of favipiravir in real samples using HPLC/UV with sufficient sensitivity. The effects of several variables on extraction efficiency were investigated, including type of extractant, amount of extractant, type of disperser and disperser volume. The maximum enrichment was attained using 50 mg of the Gd-magnetic ionic liquid (MIL) and 150 μl of tetrahydrofuran. The Gd-based MIL could form a supramolecular assembly in the presence of tetrahydrofuran, which enhanced the extraction efficiency of favipiravir. The developed method was validated according to US Food and Drug Administration bioanalytical method validation guidelines. The coefficient of determination was 0.9999, for a linear concentration range of 25 to 1.0 × 10⁵ ng/ml. The percentage recovery (accuracy) varied from 99.83 to 104.2%, with RSD values (precision) ranging from 4.07 to 11.84%. The total extraction time was about 12 min and the HPLC analysis time was 5 min. The method was simple, selective and sensitive for the determination of favipiravir in real human plasma.     

Development and validation of LC–MS/MS method for amlexanox in rat plasma and its application in preclinical pharmacokinetics

Amlexanox, an anti-inflammatory and anti-allergic agent, has been widely used clinically for the treatment of canker sores, asthma, and allergic rhinitis. Recently, amlexanox has received considerable attention in curing nonalcoholic fatty liver diseases and hepatitis virus infection. Herein, we first established a sensitive high-performance liquid chromatography-tandem mass spectrum (LC–MS/MS) method for the determination of amlexanox in rat plasma. Propranolol was used as the internal standard (IS). Using a simple protein precipitation method, the amlexanox and IS were separated with Capcell Pak C18 column (2.0 × 50 mm, 5 μm) and eluted with water and acetonitrile each containing 0.1% formic acid using gradient elution condition at a flow rate of 0.4 mL·min⁻¹. Amlexanox and IS were detected by a triple quadrupole mass in multiple reactive monitoring (MRM) under the transitions of m/z 299.2 → 281.2 and m/z 259.9 → 116.1 with positive electrospray ionization, respectively. The calibration curves of amlexanox were established with the range of 50 to 2000 ng·mL⁻¹ (r² > 0.99). The validation method consisted of selectivity, accuracy, precision, carryover effect, matrix effect, recovery, dilution effect, and stability. The fully validated method was successfully applied to the pharmacokinetic study of amlexanox in Wistar rats.     

Insights into MWCNTs/polyimide nanocomposites: from synthesis to application as free-standing flexible electrodes in low-cost micro-supercapacitors

In the pursuit to enlarge the library of polyimide materials for energy applications, new polyimide/MWCNTs composite films have been developed by MWCNTs-assisted polycondensation reaction of a hydroxyl and triphenylmethane-containing diamine with benzophenone tetracarboxylic dianhydride targeting to highlight their electrical storage capability as flexible electrodes in micro-supercapacitors (mSCs). The Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance, UV–vis, fluorescence, and Raman spectroscopies were used to demonstrate the evolution of interfacial interactions between MWCNTs and the precursors (diamine monomer and intermediate polyamidic acid) and polyimide matrix that proved to be the origin of MWCNTs homogeneous dispersion. Thus, composite films incorporating 1, 3, 5, and 10 w.t.% MWCNTs were obtained and thoroughly investigated with regard to their morphology, mechanical behavior, thermal stability, and electrical conductivity. The electrochemical performance of these composites was first analyzed in a classical three-electrode cell by cyclic voltammetry and galvanostatic charge-discharge in both aqueous and organic electrolyte systems. By far, the best electrical storage capacity was obtained with the composite polyimide film containing 10% MWCNTs that was further used as both active material and current collector in a flexible symmetric mSC realized by a straightforward and low-cost procedure. In the attempt to better exploit the advantages of this composite film, it was layered with a graphite-containing paint and tested as an electrode in a flexible mSC, which provided satisfactory results. To our knowledge, this is the first report on the electrical charge storage capability of a polyimide/MWCNTs free-standing film as a flexible electrode in mSCs, which do not require time- and resource-consuming processing steps.     

Anti-fibrosis attributes: UHPLC-MS/MS-based pharmacokinetics profiling of a novel autotaxin inhibitor with excellent in vivo efficacy in rat

3,4-Difluorobenzyl(1-ethyl-5-(4-((4-hydroxypiperidin-1-yl)-methyl)thiazol-2-yl)-1H-indol-3-yl)carbamate (NAI59), a small molecule with outstanding therapeutic effectiveness to anti-pulmonary fibrosis, was developed as an autotaxin inhibitor candidate compound. To evaluate the pharmacokinetics and plasma protein binding of NAI59, a UPLC–MS/MS method was developed to quantify NAI59 in plasma and phosphate-buffered saline. The calibration curve linearity ranged from 9.95 to 1990.00 ng/mL in plasma. The accuracy was −6.8 to 5.9%, and the intra- and inter-day precision was within 15%. The matrix effect and recovery, as well as dilution integrity, were within the criteria. The chromatographic and mass spectrometric conditions were also feasible to determine phosphate-buffered saline samples, and it has been proved that this method exhibits good precision and accuracy in the range of 9.95–497.50 ng/mL in phosphate-buffered saline. This study is the first to determine the pharmacokinetics, absolute bioavailability, and plasma protein binding of NAI59 in rats using this established method. Therefore, the pharmacokinetic profiles of NAI59 showed a dose-dependent relationship after oral administration, and the absolute bioavailability in rats was 6.3%. In addition, the results of protein binding showed that the combining capacity of NAI59 with plasma protein attained 90% and increased with the increase in drug concentration.     

A branch-and-bound method for the minimum k−enclosing ball problem

The minimum k-enclosing ball problem seeks the ball with smallest radius that contains at least k of m given points. This problem is NP-hard. We present a branch-and-bound algorithm on the tree of the subsets of k points to solve this problem. Our method is able to solve the problem exactly in a short amount of time for small and medium sized datasets.     

Direct visualization of the nanoscopic three‐phase structure and stiffness of NBR/PVC blends by AFM nanomechanical mapping

The PeakForce Quantitative Nanomechanical Mapping based on atomic force microscope (AFM) is employed to first visualize and then quantify the elastic properties of a model nitrile rubber/poly(vinyl chloride) (NBR/PVC) blend at the nanoscale. This method allows us to consistently observe the changes in mechanical properties of each phase in polymer blends. Beyond measuring and discriminating elastic modulus and adhesion forces of each phase, we tune the AFM tips and the peak force parameters in order to reliably image samples. In view of viscoelastic difference in each phase, a three‐phase coexistence of an unmixed NBR phase, the mixed phase, and PVC microcrystallites is directly visualized in NBR/PVC blends. The nanomechanical investigation is also capable of recognizing the crosslinked rubber phase in cured rubber. The contribution of the mixed phase was quantified and it was found that the mechanical properties of blends are mainly determined by the homogeneity and stiffness of the mixed phase. This study furthers our understanding the structure–mechanical property relationship of thermoplastic elastomers, which is important for their potential design and applications. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019 , 57, 662–669     

Determination of sulfa antibiotic residues in river and particulate matter by field-amplified sample injection-capillary zone electrophoresis

In the present research, field-amplified sample injection–CZE (FASI–CZE) coupled with a diode array detector was established to determine trace level sulfa antibiotic. Sulfathiazole, sulfadiazine, sulfamethazine, sulfadimethoxine, sulfamethoxazole, and sulfisoxazole were selected as analytes for the experiments. The background electrolyte solution consisted of 70.0 mmol/L borax and 60.0 mmol/L boric acid (including 10% methanol, pH 9.1). The plug was 2.5 mmol/L borax, which was injected into the capillary at a pressure of 0.5 psi for 5 s. Then the sample was injected into the capillary at an injection voltage of –10 kV for 20 s. The electrophoretic separation was carried out under a voltage of +19 kV. The capillary temperature was maintained at 20˚C throughout the analysis, and six sulfonamides were completely separated within 35 min. Compared with pressure injection-CZE, the sensitivity of FASI-CZE was increased by 6.25–10.0 times, and the LODs were reduced from 0.2–0.5 to 0.02–0.05 μg/mL. The method was applied to the determination of sulfonamides in river water and particulate matter samples. The recoveries were 78.59–106.59%. The intraday and interday precisions were 2.89–7.35% and 2.77–7.09%, respectively. This provides a simpler and faster method for the analysis of sulfa antibiotic residues in environmental samples.     

An approach of dynamic mesh adaptation for simulating 3‐dimensional unsteady moving‐immersed‐boundary flows

In this paper, we present an approach of dynamic mesh adaptation for simulating complex 3‐dimensional incompressible moving‐boundary flows by immersed boundary methods. Tetrahedral meshes are adapted by a hierarchical refining/coarsening algorithm. Regular refinement is accomplished by dividing 1 tetrahedron into 8 subcells, and irregular refinement is only for eliminating the hanging points. Merging the 8 subcells obtained by regular refinement, the mesh is coarsened. With hierarchical refining/coarsening, mesh adaptivity can be achieved by adjusting the mesh only 1 time for each adaptation period. The level difference between 2 neighboring cells never exceeds 1, and the geometrical quality of mesh does not degrade as the level of adaptive mesh increases. A predictor‐corrector scheme is introduced to eliminate the phase lag between adapted mesh and unsteady solution. The error caused by each solution transferring from the old mesh to the new adapted one is small because most of the nodes on the 2 meshes are coincident. An immersed boundary method named local domain‐free discretization is employed to solve the flow equations. Several numerical experiments have been conducted for 3‐dimensional incompressible moving‐boundary flows. By using the present approach, the number of mesh nodes is reduced greatly while the accuracy of solution can be preserved.     

Concurrent multiresponse non-linear screening: Robust profiling of webpage performance

Profiling engineered data with robust mining methods continues attracting attention in knowledge engineering systems. The purpose of this article is to propose a simple technique that deals with non-linear multi-factorial multi-characteristic screening suitable for knowledge discovery studies. The method is designed to proactively seek and quantify significant information content in engineered mini-datasets. This is achieved by deploying replicated fractional-factorial sampling schemes. Compiled multi-response data are converted to a single master-response effectuated by a series of distribution-free transformations and multi-compressed data fusions. The resulting amalgamated master response is deciphered by non-linear multi-factorial stealth stochastics intended for saturated schemes. The stealth properties of our method target processing datasets which might be overwhelmed by a lack of knowledge about the nature of reference distributions at play. Stealth features are triggered to overcome restrictions regarding the data normality conformance, the effect sparsity assumption and the inherent collapse of the ‘unexplainable error’ connotation in saturated arrays. The technique is showcased by profiling four ordinary controlling factors that influence webpage content performance by collecting data from a commercial browser monitoring service on a large scale web host. The examined effects are: (1) the number of Cascading Style Sheets files, (2) the number of JavaScript files, (3) the number of Image files, and (4) the Domain Name System Aliasing. The webpage performance level was screened against three popular characteristics: (1) the time to first visual, (2) the total loading time, and (3) the customer satisfaction. Our robust multi-response data mining technique is elucidated for a ten-replicate run study dictated by an L₉(3⁴) orthogonal array scheme where any uncontrolled noise embedded contribution has not been necessarily excluded.