A novel high-performance thin-layer chromatographic (HPTLC) analytical method has been developed and optimized for the quantification of quetiapine fumarate (QF) and its two genotoxic impurities in drug substance and drug product. The desired separation was achieved on 60F254 pre-coated HPTLC plates using combination of green solvents, ethyl acetate‒ethanol‒n-heptane (5:1:4, V/V) as developing solvents. The detection wavelength used for quantification was 229 nm. QF and its two related genotoxic impurities, namely, 2-chloroaniline and 2-aminodiphenylsulfide, were well resolved from one another with retention factor values of 0.13 ± 0.02, 0.57 ± 0.02 and 0.76 ± 0.02, respectively. The optimized method was validated according to the guidelines laid down by the International Council for Harmonisation. The linearity was determined in the range of 100–600 ng/spot for QF and 10‒60 ng/spot for its two related genotoxic impurities; R2 ≥ 0.993. The method exhibited precision along with good accuracy, where 0.51, 0.86 and 1.86. The percentage recoveries obtained for 2-chloroaniline and 2-aminodiphenylsulfide were 99.04‒101.04%. The developed method can be successfully used for the analysis of drug samples.
Differential thermal analysis (DTA) has been employed to investigate the effect of Ge addition on the glass transition behavior and crystallization kinetics of Sb10Se90?xGex (x = 0, 19, 21, 23, 25, 27) alloys. The three characteristic temperatures viz. glass transition (Tg), crystallization (Tc), and melting (Tm) have been determined and found to vary with the heating rates and Ge content. Thermal stability and glass forming tendency have been evaluated in terms of ΔT (= Tc ? Tg) and reduced glass transition temperature. The activation energies for glass transition and crystallization have been used to analyze the nucleation and growth process. The activation energy analysis also determines the suitability of alloys to be used in switching applications. Results have been interpreted in terms of bond energies and structural transformations in the investigated alloys. 相似文献
The platinum(II) complexes with N,S-donor ligand have been synthesised and characterised by physiological techniques like elemental, electronic, Fourier transform infrared, hydrogen-1 nuclear magnetic resonance (1H NMR) and liquid chromatography–mass spectrometry spectra. The synthesised complexes have been checked for their DNA binding ability by absorption titration and viscosity measurement, and the results show that the complexes binds to herring sperm DNA (HS DNA) via covalent mode of binding. The DNA cleavage activity of synthesised complexes has been carried out by gel electrophoresis experiment using supercoiled form of pUC19 DNA, showing the unwinding of the negatively charged supercoiled DNA. Brine shrimp (Artemia cysts) lethality bioassay technique has been applied for the determination of toxic property of synthesised complexes in terms of micromolars. 相似文献
A set of structurally related O-methylated flavonoid natural products isolated from Senecio roseiflorus (1), Polygonum senegalense (2 and 3), Bhaphia macrocalyx (4), Gardenia ternifolia (5), and Psiadia punctulata (6) plant species were characterized for their interaction with human monoamine oxidases (MAO-A and -B) in vitro. Compounds 1, 2, and 5 showed selective inhibition of MAO-A, while 4 and 6 showed selective inhibition of MAO-B. Compound 3 showed ~2-fold selectivity towards inhibition of MAO-A. Binding of compounds 1–3 and 5 with MAO-A, and compounds 3 and 6 with MAO-B was reversible and not time-independent. The analysis of enzyme-inhibition kinetics suggested a reversible-competitive mechanism for inhibition of MAO-A by 1 and 3, while a partially-reversible mixed-type inhibition by 5. Similarly, enzyme inhibition-kinetics analysis with compounds 3, 4, and 6, suggested a competitive reversible inhibition of MAO-B. The molecular docking study suggested that 1 selectively interacts with the active-site of human MAO-A near N5 of FAD. The calculated binding free energies of the O-methylated flavonoids (1 and 4–6) and chalcones (2 and 3) to MAO-A matched closely with the trend in the experimental IC50′s. Analysis of the binding free-energies suggested better interaction of 4 and 6 with MAO-B than with MAO-A. The natural O-methylated flavonoid (1) with highly potent inhibition (IC50 33 nM; Ki 37.9 nM) and >292 fold selectivity against human MAO-A (vs. MAO-B) provides a new drug lead for the treatment of neurological disorders. 相似文献
Incorporation of isotopes has long been used as a research tool to label carbons and elucidate biochemical pathways. More recently, H→D exchange has led to analogs of therapeutic agents with improved metabolic stability and properties. Such compounds also have the potential for an improved drug/drug interaction profile and may even avoid the formation of toxic metabolites. Hence, a clear need for an efficient access to deuterated intermediates on large scale has emerged. In the context of an ongoing drug discovery program, we required large quantities of morpholine-d8. We herein report the successful optimization of a one-pot process allowing a near complete exchange of all methylene hydrogens in morpholine to deuterium atoms using D2O as the sole source of deuterium and Raney Nickel as catalyst. This facile and safe protocol will be used to scale up the synthesis of morpholine-d8 in due course. 相似文献
A novel one‐pot, three‐component diastereo‐ and enantioselective synthesis of spiropyrazolones has been developed involving the aldol condensation of an enal to generate α,β‐unsaturated pyrazolones, which react with a second equivalent of enal through an N‐heterocyclic carbene (NHC)‐catalyzed [3+2] annulation. The desired spirocyclopentane pyrazolones are obtained in moderate to good yields and good to excellent stereoselectivities. Alternatively, starting from cyclic 1,3‐diketones, 2,5‐chromenediones are available through [2+4] annulation. 相似文献
We consider here the genericity aspects of spacetime singularities that occur in cosmology and in gravitational collapse.
The singularity theorems (that predict the occurrence of singularities in general relativity) allow the singularities of gravitational
collapse to be either visible to external observers or covered by an event horizon of gravity. It is shown that the visible
singularities that develop as final states of spherical collapse are generic. Some consequences of this fact are discussed.
相似文献