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.     

Interface and defects engineering for multilayer laser coatings

High-reflective multilayer laser coatings are widely used in advanced optical systems from high power laser facilities to high precision metrology systems. However, the real interface quality and defects will significantly affect absorption/scattering losses and laser induced damage thresholds of multilayer coatings. With the recent advances in the control of coating design and deposition processes, these coating properties can be significantly improved when properly engineered the interface and defects. This paper reviews the recent progress in the physics of laser damage, optical losses and environmental stability involved in multilayer reflective coatings for high power nanosecond near-infrared lasers. We first provide an overview of the layer growth mechanisms, ways to control the microstructures and reduce layer roughness, as well as the nature of defects which are critical to the optical loss and laser induced damage. Then an overview of interface engineering based on the design of coating structure and the regulation of deposition materials reveals their ability to improve the laser induced damage threshold, reduce the backscattering, and realize the desirable properties of environmental stability and exceptional multifunctionality. Moreover, we describe the recent progress in the laser damage and scattering mechanism of nodule defects and give the approaches to suppress the defect-induced damage and scattering of the multilayer laser coatings. Finally, the present challenges and limitations of high-performance multilayer laser coatings are highlighted, along with the comments on likely trends in future.     

Water-assisted mechanical testing of polymeric thin-films

Thin films with a nanometer-scale thickness are of great interest to both scientific and industrial communities due to their numerous applications and unique behaviors different from the bulk. However, the understanding of thin-film mechanics is still greatly hampered due to their intrinsic fragility and the lack of commercially available experimental instruments. In this review, we first discuss the progression of thin-film mechanical testing methods based on the supporting substrate: film-on-solid substrate method, film-on-water tensile tests, and water-assisted free-standing tensile tests. By comparing past studies on a model polymer, polystyrene, the effect of different substrates and confinement effect on the thin-film mechanics is evaluated. These techniques have generated fruitful scientific knowledge in the field of organic semiconductors for the understanding of structure–mechanical property relationships. We end this review by providing our perspective for their bright prospects in much broader applications and materials of interest.     

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.     

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     

A unified theory for brittle and ductile shear mode fracture

A unified theory captures both brittle and ductile fracture. The fracture toughness is proportional to the applied stress squared and the length of the crack. For purely brittle solids, this criterion is equivalent to Griffith's theory. In other cases, it provides a theoretical basis for the Irwin-Orowan formula. For purely ductile solids, the theory makes direct contact with the Bilby-Cottrell-Swinden model. The toughness is highest in ductile materials because the shielding dislocations in the plastic zone provide additional resistance to crack growth. This resistance is the force opposing dislocation motion, and the Peach-Koehler force overcomes it. A dislocation-free zone separates the plastic zone from and the tip of the crack. The dislocation-free zone is finite because molecular forces responsible for the cohesion of the surfaces near the crack tip are not negligible. At the point of crack growth, the length of the dislocation-free zone is constant and the shielding dislocations advance in concert. As in Griffith's theory, the crack is in unstable equilibrium. The theory shows that a dimensionless variable controls the elastoplastic behaviour. A relationship for the size of the dislocation-free zone is derived in terms of the macroscopic and microscopic parameters that govern the fracture.