Simultaneous determination of colchicine and febuxostat in rat plasma: Application in a rat pharmacokinetic study

A selective, sensitive and rapid LC–MS/MS method has been developed and validated as per US Food and Drug Administration regulatory guidelines for the simultaneous quantitation of colchicine and febuxostat in rat plasma. Colchicine and febuxostat were extracted from the rat plasma using 10% tert-butyl methyl ether in ethyl acetate using colchicine-d₆ as an internal standard (IS). The chromatographic separation of colchicine, febuxostat and the IS was achieved using a mobile phase comprising 5 mm ammonium formate and 0.025% formic acid in acetonitrile (20:80, v/v) in isocratic mode on an Eclipse XDB-C₁₈ column. The injection volume and flow rate were 5.0 μl and 0.9 ml/min, respectively. Colchicine and febuxostat were detected by positive electrospray ionization in multiple reaction monitoring mode using transition pairs (Q1 → Q3) of m/z 400.10 → 358.10 and 317.05 → 261.00, respectively. The assay was linear in the ranges of 0.25–254 and 2.60–622 ng/ml for colchicine and febuxostat, respectively. The inter- and intra-day precision values were 0.58–13.0 and 1.03–4.88% for colchicine and febuxostat, respectively. No matrix or carryover effects were observed during the validation. Both analytes were stable on the bench-top, in the autosampler and in storage (freeze–thaw cycles and long-term storage at −80 ° C). A pharmacokinetic study in rats was performed to show the applicability of the validated method.     

Spectroscopy of50V with (p,nγ) reaction

Information on the low-lying levels up to ～1.9 MeV excitation of the doubly odd nucleus⁵⁰V has been obtained through the Ge (Li)-Ge (Li) coincidence study with the⁵⁰Ti(p, nγ)⁵⁰V reaction. Branching ratios have been measured and tentative spin-parity assignments have been made. A detailed comparison with other measurements reported recently has also been made. Using the lowest seniority wave functions with (f_7/2) _p ³ (f _7/2) _n ^?1 configuration, energy levels and electromagnetic properties have been calculated. These have been compared with the present and earlier experimental data.     

Effect of pyridine on infrared absorption spectra of copper phthalocyanine

Infrared absorption spectra of copper phthalocyanine in KBr pellet and pyridine solution in 400-1625 and 2900-3200 cm(-1)regions are reported. In the IR spectra of solid sample, presence of weak bands, which are forbidden according to the selection rules of D4h point group, is explained on the basis of distortion in the copper phthalocyanine molecule caused by the crystal packing effects. Observation of a new band at 1511 cm(-1) and change in intensity of some other bands in pyridine are interpreted on the basis of coordination of the solvent molecule with the central copper ion.     

New developments in the preparation of anion exchange media based on hyperbranched condensation polymers

We have developed a number of new anion exchange stationary phases based on synthesis of hyperbranched condensation polymers prepared in situ on surface sulfonated wide pore, low surface area ethylvinylbenzene-divinylbenzene substrate beads. These new stationary phases are synthesized by exposing the substrate beads to a mixture containing one of several different diepoxides and methyl amine followed by exposure in an alternating fashion to diepoxide and then methyl amine in a repetitive manner. With each cycle of reaction with first diepoxide and then methyl amine, the capacity of the stationary phase doubles, allowing for the synthesis of high-capacity materials. These new phases are stable to hydrolysis in concentrated acid and base. They exhibit exceptionally low levels of hydrophobic interaction with anionic species commonly of interest in the analysis of environmental samples.     

Comparative study on different carbon nanotube materials in terms of transparent conductive coatings

We compared conductive transparent carbon nanotube coatings on glass substrates made of differently produced single-wall (SWNT), double-wall, and multiwall carbon nanotubes. The airbrushing approach and the vacuum filtration method were utilized for the fabrication of carbon nanotube films. The optoelectronic performance of the carbon nanotube film was found to strongly depend on many effects including the ratio of metallic-to-semiconducting tubes, dispersion, length, diameter, chirality, wall number, structural defects, and the properties of substrates. The electronic transportability and optical properties of the SWNT network can be significantly altered by chemical doping with thionyl chloride. Hall effect measurements revealed that all of these thin carbon nanotube films are of p-type probably due to the acid reflux-based purification and atmospheric impurities. The competition between variable-range hoping and fluctuation-assisted tunneling in the functionized carbon nanotube system could lead to a crossover behavior in the temperature dependence of the network resistance.     

Utilization of Cheese Whey Using Synergistic Immobilization of β-Galactosidase and <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> Cells in Dual Matrices

Whey is a byproduct of the dairy industry, which has prospects of using as a source for production of various valuable compounds. The lactose present in whey is considered as an environmental pollutant and its utilization for enzyme and fuel production, may be effective for whey bioremediation. The dairy yeast Kluyveromyces marxianus have the ability to utilize lactose sharply as the major carbon source for the production of the enzyme. Five strains were tested for the production of the β-galactosidase using whey. The maximum β-galactosidase activity of 1.74 IU/mg dry weight was achieved in whey using K. marxianus MTCC 1389. The biocatalyst was further immobilized on chitosan macroparticles and exhibited excellent functional activity at 35 °C. Almost 89 % lactose hydrolysis was attained for concentrated whey (100 g/L) and retained 89 % catalytic activity after 15 cycles of reuse. Finally, β-galactosidase was immobilized on chitosan and Saccharomyces cerevisiae on calcium alginate, and both were used together for the production of ethanol from concentrated whey. Maximal ethanol titer of 28.9 g/L was achieved during fermentation at 35 °C. The conclusions generated by employing two different matrices will be beneficial for the future modeling using engineered S. cerevisiae in scale-up studies.     

Pyrazolo[1,5-a]pyrimidines. A combined multinuclear magnetic resonance (1H, 13C, 15N, 19F) and DFT approach to their structural assignment

Multinuclear magnetic resonance spectroscopy together with GIAO-DFT calculations allowed establishment of the structure of the products obtained by condensation of 3(5)-amino-4-phenyl-1H-pyrazole and beta-dicarbonyl compounds bearing a trifluoromethyl group. They are 3-phenyl-5-(R)-7-trifluoromethylpyrazolo[1,5-a]pyrimidines.     

Leveraging an enzyme/artificial substrate system to enhance cellular persulfides and mitigate neuroinflammation

Persulfides and polysulfides, collectively known as the sulfane sulfur pool along with hydrogen sulfide (H₂S), play a central role in cellular physiology and disease. Exogenously enhancing these species in cells is an emerging therapeutic paradigm for mitigating oxidative stress and inflammation that are associated with several diseases. In this study, we present a unique approach of using the cell''s own enzyme machinery coupled with an array of artificial substrates to enhance the cellular sulfane sulfur pool. We report the synthesis and validation of artificial/unnatural substrates specific for 3-mercaptopyruvate sulfurtransferase (3-MST), an important enzyme that contributes to sulfur trafficking in cells. We demonstrate that these artificial substrates generate persulfides in vitro as well as mediate sulfur transfer to low molecular weight thiols and to cysteine-containing proteins. A nearly 100-fold difference in the rates of H₂S production for the various substrates is observed supporting the tunability of persulfide generation by the 3-MST enzyme/artificial substrate system. Next, we show that the substrate 1a permeates cells and is selectively turned over by 3-MST to generate 3-MST-persulfide, which protects against reactive oxygen species-induced lethality. Lastly, in a mouse model, 1a is found to significantly mitigate neuroinflammation in the brain tissue. Together, the approach that we have developed allows for the on-demand generation of persulfides in vitro and in vivo using a range of shelf-stable, artificial substrates of 3-MST, while opening up possibilities of harnessing these molecules for therapeutic applications.

A persulfide/hydrogen sulfide generation strategy through artificial substrates for 3-mercaptopyruvate sulfurtransferase (3-MST) is reported, which enhances cellular persulfides, attenuates reactive oxygen species (ROS), and alleviates inflammation.     

Multi parameter optimization of Raman Fiber Amplifier using genetic algorithm for S band dense wavelength division multiplexed system

A simple genetic algorithm is implemented to perform multi parameter optimization of Raman Fiber Amplifier for 100 channel S band dense wavelength division multiplexed system at 25 GHz interval. A cost effective system using single Raman pump is investigated aiming at maximum average gain. The single counter propagating pump is optimized to frequency of 211.528 THz and 652.93 mW power level with optimum Raman fiber length of 44.064 Km. There is evidence to show that the optimum solution presents a small gain variation (less than 3 dB) over an effective bandwidth covering 197–199.475 THz. The optimized configuration enabled an adequate system performance in terms of acceptable Q-factor (19.52 dB) and BER (1.46 × 10⁻²¹).     

Palladium-catalyzed 1,1-difunctionalization of ethylene

The 1,1-difunctionalization of ethylene, with aryl/vinyl/heteroaryl transmetalating agents and vinyl electrophiles, is reported. The reaction is high-yielding under a low pressure of ethylene, and regioselectivity is generally high for the 1,1-disubstituted product. The process is highlighted by the use of heteroaromatic cross-coupling reagents, which have not been competent reaction partners in previously reported efforts.