Synthesis and Spectroscopic Structural Elucidation of New Quinoxaline Derivatives

A quinoxaline‐2,3‐dione derivative was synthesized, and its chemical structure was determined through spectral analysis. Alkylation of this compound under phase transfer catalysis (PTC) conditions yielded monoalkylated and diakylated adducts. The monolalkylation process was shown to be regioselective occurring on the quinoxalic nitrogen atom rather than on its pyrazolic analogue. The full characterization of the synthesized compounds was studied by concerted use of NMR and MS techniques. Assignments of proton and carbon atoms were achieved through analysis of the 1D ¹H and ¹³C NMR spectra combined with homo‐ and hetero-nuclear 2D NMR experiments. Determination of the alkylation site was achieved through long‐range proton–carbon coupling correlations spectroscopy.     

Development and application of a validated stability-indicating HPLC method for simultaneous determination of granisetron hydrochloride, benzyl alcohol and their main degradation products in parenteral dosage forms

A simple, rapid and sensitive reversed phase high performance liquid chromatographic method using photodiode array detection was developed and validated for the simultaneous determination of granisetron hydrochloride, benzyl alcohol, 1-methyl-1H-indazole-3-carboxylic acid (the main degradation product of granisetron) and benzaldehyde (the main degradation product of benzyl alcohol) in granisetron injections. The separation was achieved on Hypersil BDS C8 (250 mm × 4.6 mm i.d., 5 μm particle diameter) column using a mobile phase consisted of acetonitrile:0.05 M KH₂PO₄:triethylamine (22:100:0.15) adjusted to pH 4.8. The column was maintained at 25 °C and 20 μL of solutions was injected. Photodiode array detector was used to test the peak purity and the chromatograms were extracted at 210 nm. Naphazoline hydrochloride was used as internal standard. The method was validated with respect to specificity, linearity, accuracy, precision, limit of quantitation and limit of detection. The validation acceptance criteria were met in all cases. Identification of the pure peaks was carried out using library match programmer and wavelengths of derivative optima of the spectrograms of the peaks. The method was successfully applied to the determination of the investigated drugs and their degradation products in different batches of granisetron injections. The method was proved to be sensitive for the determination down to 0.03 and 0.01% of granisetron degradation product and benzaldehyde, respectively, which are far below the compendia limits for testing these degradation products in their corresponding intact drugs.     

Measurement of thermophysical properties of polyvinyl alcohol complexed with some metal ions

Polyvinyl alcohol (PVA)-Cu(II) and PVA-Cr(III) complexes were prepared with different concentrations of CuC1₂ and Cr(NO₃)₃ salts. The structures of the obtained complexes were investigated using UV spectroscopy and x-ray analysis. The thermal properties (volumetric heat capacity, thermal diffusivity, and thermal conductivity) of aqueous solutions of PVA-metal complexes have been measured using the hot-wire (and strip) technique as a function of temperature (20°-80°C). The results show that the values of the thermal properties depend on the type and the concentration of metal ions bound to the polymeric chains of PVA and the temperatures. However, a considerable increase in the values of the thermal properties was observed for PVA-Cu(II) complex. The type of metal salt under investigation affects the structure of PVA. The complex of PVA-Cr(III) is more thermally stable than the complex of PVA with Cum. However, both polymer-metal complexes showed good properties which may make them acceptable for some practical uses.     

Biopolymer-layered polysilicate micro/nanocomposite based on chitosan intercalated in magadiite

On the basis of their high adsorption and cation exchange capacity, swelling potential and low toxicity, layered sodium silicate magadiite (Na–magadiite) is an attractive solid for intercalation of polymers. This study envisages the intercalation of cationic biopolymer chitosan (Chit) in Na–magadiite to prepare a Chit/magadiite micro/nanocomposite. Characterisation of starting-magadiite, pure chitosan and Chit/magadiite were investigated using powder X-ray diffraction analysis (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy and thermal analysis. XRD confirmed that the chitosan had been intercalated into the interlayer space of magadiite by increasing the basal spacing, d₀₀₁ from 15.6 Å to 21.45 Å. The presence of characteristic bands of biopolymer and layered silicate in Chit/magadiite were confirmed by FTIR analysis. The thermal stability of micro/nanocomposite was evaluated by thermogravimetry analysis. The results suggested the formation of electrostatic interactions by protonated amine groups with the negatively charged magadiite surface as well as intercalation in the form of a predominant monolayer arrangement of chitosan chains in layered silicate magadiite.     

Electrospray tandem mass spectrometric analysis of novel synthetic quinoxalinone derivatives

Electrospray ionization tandem mass spectrometry (ESI-MS/MS) using a hybrid QqToF-MS/MS instrument has aided the structural characterization and differentiation of a novel series of medicinal synthetic 1-N-glycoside-quinoxalinone derivatives. These derivatives 7 and 8 are formed by an amino bond between the cyclic N-1 of the quinoxaline moiety and the C-6 position of a fully protected methyl or allyl alpha-D-mannofuranoside 3 and 4, and subsequent deprotection of the mannopyranoside moiety. In general the novel synthetic quinoxaline derivatives afforded the protonated molecules in ESI. The breakdown routes of the protonated molecules were rationalized by conducting low-energy CID-MS/MS analyses. In addition, re-confirmation of the various established fragmentation routes was achieved by conducting a series of ESI-CID-QqTof-MS/MS product ion scans on various selected precursor ions, which were initiated by CID in the atmospheric pressure/vacuum interface using a higher declustering potential. ESI-QqToF-MS/MS analysis has proven to be a specific and very sensitive method for the structural identification in the gas phase of these novel glycoquinoxalinamine derivatives.     

Hierarchically porous nanostructures through phosphonate-metal alkoxide condensation and growth using functionalized dendrimeric building blocks

Controlled titanium alkoxide mineralization in the presence of phosphonated, dendrimeric nano-building blocks provides a new family of hierarchically porous dendrimer-bridged titanium dioxide materials.     

Spectrofluorimetric determination of drugs containing active methylene group using N1-methyl nicotinamide chloride as a fluorigenic agent

A spectrofluorimetric method was described for the determination of drugs containing active methylene groups adjacent to carbonyl groups. The method was applied successfully to the determination of three life saving cardiovascular drugs, with narrow therapeutic indices: pentoxifylline (I), propafenone hydrochloride (II) and acebutolol hydrochloride (III), in laboratory-prepared mixtures, in commercial tablets and in plasma samples. The method involved the reaction of each of the tested drugs with N1-methyl nicotinamide chloride (NMNCl) in the presence of alkali, followed by addition of formic acid, where highly fluorescent reaction products were produced. The produced fluorescence were measured quantitatively at 472 nm (lambdaex 352 nm), 409 nm (lambdaex 310 nm) and 451 nm (lambdaex 266 nm) for (I), (II), and (III) respectively. The method was linear over concentration ranges of 10-1000 microg/ml , 0.2-12 microg/ml and 0.08-10 microg/ml in standard solutions for (I), (II), and (III) respectively. In spiked human plasma samples, calibration graphs were linear over concentration ranges of 20-1000 microg/ml, 0.2-15 microg/ml and 0.08-10 microg/ml for (I), (II), and (III) respectively. The method showed good accuracy, specificity and precision in both laboratory-prepared mixtures and spiked human plasma samples. The proposed method is simple, with low instrumentation requirements, suitable for quality control application, bioavailability and bioequivalency studies.     

Removal of dyes from colored textile wastewater by orange peel adsorbent: equilibrium and kinetic studies

The use of low-cost and ecofriendly adsorbents has been investigated as an ideal alternative to the current expensive methods of removing dyes from wastewater. Orange peel was collected from the fields of orange trees in the north of Iran and converted into a low-cost adsorbent. This paper deals with the removal of textile dyes from aqueous solutions by orange peel. Direct Red 23 (DR23) and Direct Red 80 (DR80) were used as model compounds. The adsorption capacity Q0 was 10.72 and 21.05 mg/g at initial pH 2. The effects of initial dye concentration (50, 75, 100, 125 mg/l), pH, mixing rate, contact time, and quantity of orange peel have been studied at 25 degrees C. The Langmuir and Freundlich models were used for this study. It was found that the experimental results show that the Langmuir equation fit better than the Freundlich equation. The results indicate that acidic pH supported the adsorption of both dyes on the adsorbent. Orange peel with concentrations of 8 and 4 g/l has shown adsorption efficiencies of about 92 and 91% for DR23 and DR80, respectively. Furthermore, adsorption kinetics of both dyes was studied and the rates of sorption were found to conform to pseudo-second-order kinetics with a good correlation (R > or = 0.998). Maximum desorption of 97.7% for DR23 and 93% for DR80 were achieved in aqueous solution at pH 2. Finally, the effect of adsorbent surface was analyzed by scanning electron microscope (SEM). SEM images showed reasonable agreement with adsorption measurements.     

Spectrofluorimetric determination of warfarin sodium by using N1-methylnicotinamide chloride as a fluorigenic agent

A spectrofluorimetric method is described for the determination of drugs containing active methylene groups adjacent to carbonyl groups. The method was applied successfully to the determination of warfarin sodium in laboratory-prepared mixtures, in commercial tablets, and in spiked human plasma samples. Finally, the method was applied to the determination of the steady-state concentration of warfarin sodium in the blood of a hospitalized patient. The method involves the reaction of warfarin sodium with 0.2 ml (0.4 x 10(-3)M) N1-methylnicotinamide chloride reagent in the presence of 3 mL 1.0N NaOH and cooling in ice for 8 min, followed by adjustment of the pH to 2.0, using formic acid and heating for 4 min, whereby a highly fluorescent reaction product is produced. The optimal wavelengths of excitation and emission were determined by using a synchronous wavelength search and found to be 284 and 354 nm, respectively. The standard curves were linear over a concentration range of 50-1500 ng/mL in both aqueous solutions and spiked human plasma samples. The mean recoveries (+/- standard deviation) were 101.157 (+/-1.33) and 95.73 (+/-1.88%) for aqueous solutions and spiked human plasma samples, respectively. The method showed good specificity and precision. The proposed method is simple and economical because of its minimal instrumentation and chemicals requirements. Nevertheless, it is highly sensitive, specific, and reproducible. Accordingly, it is suitable for quality-control applications, drug monitoring, and bioavailability and bioequivalency studies.