A sensitive UPLC-MS/MS method for the simultaneous assay and trace level genotoxic impurities quantification of SARS-CoV-2 inhibitor-Molnupiravir in its pure and formulation dosage forms using fractional factorial design

Two potential genotoxic impurities were identified (PGTIs)-viz. 4-amino-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one (PGTI-1), and 1-(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2,4(1H,3H)-one (PGTI-II) in the Molnupiravir (MOPR) synthetic routes. COVID-19 disease was treated with MOPR when mild to moderate symptoms occurred. Two (Q)-SAR methods were used to assess the genotoxicity, and projected results were positive and categorized into Class-3 for both PGTIs. A simple, accurate and highly sensitive ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method was optimized for the simultaneous quantification of the assay, and these impurities in MOPR drug substance and formulation dosage form. The multiple reaction monitoring (MRM) technique was utilized for the quantification. Prior to the validation study, the UPLC-MS method conditions were optimised using fractional factorial design (FrFD). The optimized Critical Method Parameters (CMPs) include the percentage of Acetonitrile in MP B, Concentration of Formic acid in MP A, Cone Voltage, Capillary Voltage, Collision gas flow and Desolvation temperature were determined from the numerical optimization to be 12.50 %, 0.13 %, 13.6 V, 2.6 kV, 850 L/hr and 375 °C, respectively. The optimized chromatographic separation achieved on Waters Acquity HSS T3 C18 column (100 mm × 2.1 mm, 1.8 µm) in a gradient elution mode with 0.13% formic acid in water and acetonitrile as mobile phases, column temperature kept at 35 °C and flow rate at 0.5 mL/min. The method was successfully validated as per ICH guidelines, and demonstrated excellent linearity over the concentration range of 0.5–10 ppm for both PGTIs. The Pearson correlation coefficient of each impurity and MOPR was found to be higher than 0.999, and the recoveries were in between the range of 94.62 to 104.05% for both PGTIs and 99.10 to 100.25% for MOPR. It is also feasible to utilise this rapid method to quantify MOPR accurately in biological samples

Enhanced Multiferroic Properties of YMnO3 Ceramics Fabricated by Spark Plasma Sintering Along with Low-Temperature Solid-State Reaction

Based on precursor powders with a size of 200–300 nm prepared by the low-temperature solid-state reaction method, phase-pure YMnO3 ceramics are fabricated using spark plasma sintering (SPS). X-ray diffraction (XRD) and scanning electron microscopy (SEM) reveal that the high-purity YMnO3 ceramics can be prepared by SPS at 1000 °C for 5 minutes with annealing at 800 °C for 2 h. The relative density of the sample is as high as 97%, which is much higher than those of the samples sintered by other methods. The present dielectric and magnetic properties are much better than those of the samples fabricated by conventional methods and SPS with ball-milling precursors, and the ferroelectric loops at room temperature can be detected. These findings indicate that the YMnO3 ceramics prepared by the low temperature solid reaction method and SPS possess excellent dielectric lossy ferroelectric properties at room temperature, and magnetic properties at low temperature (10 K), making them suitable for potential multiferroic applications

Isolation, identification, structural elucidation, and toxicity prediction using (Q)-SAR models of two degradants: AQbD-driven LC method to determine the Roxadustat impurities

ABSTRACT: Roxadustat (RDT) is the first orally administrated HIF-prolyl hydroxylase inhibitor drug used to treat anemia caused by chronic kidney disease. Two unknown degradants were detected in photolytic and oxidative stress conditions during the forced degradation study of RDT and isolated them using the preparative HPLC. The structural characterization of these impurities was confirmed using ESI-LC-MS, NMR, and FT-IR spectroscopic analysis. To evaluate the toxicity of degradants, (Q)-SAR models such as Derek and Sarah model were utilized. The current study aims to develop a stability-indicating related substances quantification method in RDT along with degradant impurities by implementing AQbD principles. The Box-Behnken Design (BBD) was utilized to optimize the final analytical method conditions. p-values for the model and lack of fit were 0.05, respectively. The optimized CMPs are 30:70 (v/v) ACN: Methanol in mobile phase-B, 50:50 mobile phase-A & B in the initial gradient program, 0.95 mL/min of flow rate, and 40 °C as column oven temperature. Agilent Zorbax XDB-C8, (250 × 4.6) mm, 5 μm analytical column was used to separate the desired components from the sample matrix peaks and themselves. The optimized method was validated in compliance with regulatory requirements. The recoveries for all the impurities ranged from 96.8% to 99.7%, with an%RSD 0.998. The current method can be used in quality-control laboratories to quantify RDT impurities without any developmental trials

Hybrid gel polymer electrolyte based on 1-methyl-1-Propylpyrrolidinium Bis(Trifluoromethanesulfonyl) imide for flexible and shape-variant lithium secondary batteries

Lithium ion conducting polymer electrolytes with broad electrochemical stability, good mechanical strength, high thermal stability, and easy processability are necessary for all-solid-state and shape-variant lithium secondary batteries. Hybrid gel polymer electrolytes incorporating an ionic liquid have been attracting attention for application in solid-state lithium secondary batteries owing to their superior thermal properties compared to conventional electrolyte systems. In this study, a variety of polymer electrolytes based on poly(vinylidene fluoride-co-hexafluoropropylene) (PVdF-HFP), lithium bis(trifluoromethanesulfonyl) imide (LiTFSI), and 1-methyl-1-propylpyrrolidinium bis(trifluoromethanesulfonyl) imide (PMPyrrTFSI) are prepared, and an in-depth study of their composition dependence and electrical properties is conducted to develop the optimum composition. The composition dependent ionic conductivity of the polymer electrolyte increases with increasing LiTFSI and PMPyrrTFSI and reaches a maximum value of 6.93 × 10−4 S cm−1 at room temperature (25 °C) when the polymer electrolyte contains 30 wt% LiTFSI and 60 wt% PMPyrrTFSI. In addition, the optimized gel polymer electrolytes consisting of PVdF-HFP/LiTFSI/PMPyrrTFSI (70/30/60 by weight, i.e., 70PVdF-HFP/30LiTFSI/60PMPyrrTFSI) look transparent and exhibit high mechanical stability and excellent thermal stability up to 420 °C. Finally, the lithium iron phosphate (LiFePO4)/lithium metal solid-state cells coupled with the optimized gel polymer electrolyte are prepared, and their discharge characteristics are studied. The 70PVdF-HFP/30LiTFSI/60PMPyrrTFSI based solid-state cell delivered a maximum discharge capacity of 151 mAh g−1 at room temperature with a good rate capability and cycling performance. © 2020 Elsevier B.V.1

Improvement of Electrochemical Performance of Lithium-ion Secondary Batteries using Double-Layered Thick Cathode Electrodes

Various steps in the electrode production process, such as slurry mixing, slurry coating, drying, and calendaring, directly affect the quality and, consequently, mechanical properties and electrochemical performance of electrodes. Herein, a new method of slurry coating is developed: Double-coated electrode. Contrary to single-coated electrode, the cathode is prepared by double coating, wherein each coat is of half the total loading mass of the single-coated electrode. Each coat is dried and calendared. It is found that the double-coated electrode possesses more uniform pore distribution and higher electrode density and allows lesser extent of particle segregation than the singlecoated electrode. Consequently, the double-coated electrode exhibits higher adhesion strength (74.7 N m−1) than the single-coated electrode (57.8 N m−1). Moreover, the double-coated electrode exhibits lower electric resistance (0.152 Ω cm−2) than the single-coated electrode (0.177 Ω cm−2). Compared to the single-coated electrode, the double-coated electrode displays higher electrochemical performance by exhibiting better rate capability, especially at higher C rates, and higher long-term cycling performance. Despite its simplicity, the proposed method allows effective electrode preparation by facilitating high electrochemical performance and is applicable for the large-scale production of high-energy-density electrodes.FALS

PHYLOGENETIC STUDY OF THREE LINES CAVIA PORCELLUS (GUINEA PIGS) PERU, ANDINA AND INTI, "EL PRADO" FARM, UNIVERSITY OF THE ARMED FORCES – ESPE IN ECUADOR

Objective: The present study was undertaken to investigate the morphological and to establish molecular relations between three lines of guinea pigs, which are phenotypically selected and form the basis for a molecular marker-assisted breeding program for the species, in the breeding farm of El Prado.Methods: Synthetic variable was used for qualitative and quantitative analysis of the study population. The DNA was extracted, amplified by PCR and then was sequenced the mitochondrial cytochrome-b gene of the lines Peru, Andina and Inti. The extracted sequences were compared with others of Cavia porcellus, and other associated genes, from neighboring countries, deposited in Genbank.Results: Phenotypic analysis was prioritized desirable characteristics for the producer. The synthetic variable generated three groups of individuals. The best group comprises of guinea pig Andina line, two of Peru, and four of Inti. Molecular characterization showed that the specimens under study achieved an average of 1101.5 bp corresponding to 98.27% of the complete mitochondrial cytochrome-b gene (1120.8bp). On comparison with Genbank sequences we observed a similarity of 98% (identical pairs), and 1.92% of variability (transition and transversion). Site analysis found 85.5% of conserved sites and 14.5% of variable sites, of which 55.48% were parsimony informative.Conclusion: These results suggest that the specimen I5 (Inti) was selected for its qualitative characteristics, good weight of reproductive age and greater intra-population genetic distance. The dendrogram for intraspecific phylogenetic inference of Cavia porcellus was robust, 100% resampling under a frequency analysis of 1000 replicates. These findings not only help in design effective breeding experiments but also help in selecting animals for experiment purposes.Keywords: Cavia porcellus, Cytochrome-b, DNA, Phylogenetic analysi

Synergistic Effect of a Dual-Salt Liquid Electrolyte with a LiNO3 Functional Additive toward Stabilizing Thin-Film Li Metal Electrodes for Li Secondary Batteries

Li metal thickness has been considered a key factor in determining the electrochemical performance of Li metal anodes. The use of thin Li metal anodes is a prerequisite for increasing the energy density of Li secondary batteries intended for emerging large-scale electrical applications, such as electric vehicles and energy storage systems. To utilize thin (20 mu m thick) Li metal anodes in Li metal secondary batteries, we investigated the synergistic effect of a functional additive (Li nitrate, LiNO3) and a dual-salt electrolyte (DSE) system composed of Li bis(fluorosulfonyl)imide (LiTFSI) and Li bis(oxalate)borate (LiBOB). By controlling the amount of LiNO3 in DSE, we found that DSE containing 0.05 M LiNO3 (DSE-0.05 M LiNO3) significantly improved the electrochemical performance of Li metal anodes. DSE-0.05 M LiNO3 increased the cycling performance by 146.3% [under the conditions of a 1C rate (2.0 mA cm(-2)), DSE alone maintained 80% of the initial discharge capacity up to the 205th cycle, whereas DSE-0.05 M LiNO3 maintained 80% up to the 300th cycle] and increased the rate capability by 128.2% compared with DSE alone [the rate capability of DSE-0.05 M LiNO3 = 50.4 mAh g(-1), and DSE = 39.3 mAh g(-1) under 7C rate conditions (14.0 mA cm(-2))]. After analyzing the Li metal surface using scanning electron microscopy and Xray photoelectron spectroscopy, we were able to infer that the stabilized solid electrolyte interphase layer formed by the combination of LiNO3 and the dual salt resulted in a uniform Li deposition during repeated Li plating/stripping processes.FALS