HPLC–PDA identification and resolution of rufinamide forced degradation impurities: A congregated chemometric expedite optimization coupled with factorials and desirability

Rufinamide is used presently to treat Lenaux–Gastaut syndrome. A full factorial design and desirability approach was investigated for the optimization of hydrolytic stress via response surface curves (RSCs). The degradation impurities were identified and resolved using reversed-phase high-performance liquid chromatography (RP-HPLC) on the Qualisil® BDS C₈ column. Acetonitrile–water (29:71, v/v) was optimized for the mobile phase and used at a flow rate of 1.0 ml/min with detection at a wavelength of 230 nm. Rufinamide showed appreciable susceptibility to hydrolysis under acidic and alkaline stress, and substantial degradation in the neutral condition. It degraded much less under oxidative stress. Exposure towards thermal and photolytic stress conditions indicated appreciable stability. The developed method was subjected to validation as per the recommendations of the International Conference on Harmonization. The proposed method showed no influence from the excipients and the degradation products. As well as good precision and accuracy in determination, the method showed a linear response between 2 and 12 μg ml⁻¹. The method was extended for determination in a human plasma sample, which resulted in excellent recovery without interference from matrix effects. The combined use of desirability and design for the optimization of acidic and alkaline hydrolytic stress led to simple and rapid analysis.     

Cyclodextrin complexation improves aqueous solubility of the antiepileptic drug,rufinamide: solution and solid state characterization of compound-cyclodextrin binary systems

Rufinamide (RUF) was characterized in terms of cyclodextrin (CD) complexation in order to improve its aqueous solubility. Binary systems of RUF with three CDs—β-cyclodextrin (β-CD), randomly methylated-β-cyclodextrin (RAMEB) and sulfobutylether-β-cyclodextrin (SBE-β-CD)—were characterized with a wide variety of analytical techniques. Liquid state characterization was carried out by complementary techniques such as nuclear magnetic resonance spectroscopy (NMR), capillary electrophoresis (CE), mass spectrometry (MS) and phase solubility studies. The latter revealed that the stability of the complexes decreased in the order of RAMEB?>?β-CD?>?SBE-β-CD. A_L-type diagrams were obtained in all cases, characteristic of 1:1 stoichiometry, with a maximum of over 15-fold increase in RUF solubility, when complexed with RAMEB. NMR Job plot and MS studies confirmed phase solubility results, regarding the binding stoichiometry. ¹H NMR and 2D ROESY investigations revealed the inclusion of the triazole moiety of RUF, confirmed by molecular modeling. Solid state complexation in 1:1 molar ratio was carried out by kneading method and investigated by differential scanning calorimetry (DSC) and infrared spectroscopy (IR). Comparative dissolution studies indicated an over two-fold improvement in dissolution efficacy of the kneaded products, when compared to the pure drug. Results of the present study might pave the way for a drug formulation with improved bioavailability.     

An Evidence-Based Review of Application Devices for Nitric Oxide Concentration Determination from Exhaled Air in the Diagnosis of Inflammation and Treatment Monitoring

The measurement of nitric oxide (NO) in exhaled air is used in diagnostics and monitoring the pathologies not only in the respiratory system but also in the oral cavity. It has shown a huge increase in its level in asthma and diseases of the oral cavity. It seems reasonable to undertake research on the impact of inflammation on the level of NO in exhaled air. The aim of the study is to make an evidence-based review of the application of NO levels in exhaled air in the diagnosis of inflammation and treatment monitoring on the basis of selected measuring devices. Methods and Results: This paper presents an example of the application of NO measurement in exhaled air in individual human systems. Selected measuring devices, their non-invasiveness, and their advantages are described. Discussion: The usefulness of this diagnostic method in pathologies of the oral cavity was noted. Conclusions: Measuring the level of NO in exhaled air seems to be a useful diagnostic method.     

Alteration in photosystem II photochemistry of thylakoids isolated from senescing leaves of wheat seedlings

Wheat seedlings, grown for 7 days in the light, were allowed to senesce in the light or dark, and the change in the photosystem II (PS II) photochemistry of chloroplasts isolated from the primary leaves of these seedlings was investigated. The decrease in oxygen evolution and the fast fluorescence results indicated that the impairment of PS II in the leaves of seedlings senescing in the light was different from that in the leaves of seedlings senescing in the dark. Thermoluminescence studies showed a structural modification in the Q_B protein of chloroplasts isolated from leaves senescing in the light and an alteration in the S state transition of chloroplasts isolated from leaves senescing in the dark.     

Analytical strategies to determine antibiotic residues in fish

The accelerated growth of aquaculture has resulted in a series of harmful effects to human health. The widespread and unrestricted use of antibiotics in this industry, to prevent bacterial infections, leads to remaining amounts in the aquatic environment. This has resulted in the emergence of antibiotic-resistant bacteria in aquaculture environments, in the increase in antibiotic resistance in fish pathogens as well as in the transfer of these resistance determinants to human pathogens. Moreover, the use of large amounts of antibiotics may lead to the presence of residual antibiotics in fish tissue and fish products. Fluoroquinolones, tetracyclines, penicillins, sulphonamides and other antibiotics, exhibiting activity against both Gram-positive and Gram-negative bacteria, are widely used for the treatment and prevention of diseases in fish. An extended and comprehensive review on the recent analytical methodologies concerning antibiotic residues in fish reported in the literature is provided in the present article. Emphasis is given on sample preparation regarding isolation and purification, chromatographic conditions and method validation according to legislation. Results of published assays are comparatively presented and criticised.     

ESR方法检测竹红菌素的半醌负离子自由基

从顺磁共振波谱检测到通过竹红菌素的光诱导还原和基态竹红菌素跟脂肪胺的电子转移两条途径所得到的自由基信号, 并由电化学还原得到同一自由基, 确认它为半醌负离子自由基。竹红菌素溶液中加入芳香胺观察不到ESR信号。它的3,10位上与醌基相邻近的羟基离解以后, 无论在基态还是在激发态都观察不到ESR信号。此外, 还从吸收光谱观察到半醌负离子自由基吸收以及竹红菌素跟脂肪胺之间的相互作用。     

Effect of the displacement reaction on the composition of the magnetic layer in electrodeposited layered nanostructures Co-Cu/Cu and Ni-Cu/Cu

Methods of stripping voltammetry, quartz microgravimetry, and x-ray-fluorescence analysis are employed to explore the copper displacement process on thin electrodeposited layers of pure cobalt and nickel and on deposits of these metals with inclusions of copper. The displacement reaction proceeds at a considerable rate on cobalt in the sulfate and sulfosalicylate solutions and virtually does not proceed on nickel in both the sulfate or sulfate-chloride solutions. An estimate of the rate of the copper displacement reaction following a change in the concentration of copper ions in the solution and in the pH of the sulfosalicylate solution is given. A decrease in the contact exchange rate is facilitated by a decrease in the concentration of copper ions in solution and their participation in the formation of complexes.     

The Behavior of Trivalent and Pentavalent Methylarsenicals in Lake Biwa

Seasonal changes in the distribution of arsenic species were observed in a dredged area in the southern basin of Lake Biwa, Japan. The concentrations of dimethylarsenic acid [DMAA(V)] became comparable with those of inorganic forms during a stratification period. DMAA(V) increased not only in the photic zone but also in the hypolimnion. In the photic zone, an increase in DMAA(V) was observed with the yearly maximum of water temperature. In the hypolimnion, the seasonal changes in methylarsenicals differed from those in surface waters. DMAA(V) maxima appeared seasonally under sub-anoxic conditions and developed regionally at the redox boundary and above the sediment surface. The DMAA(V) concentrations increased in the initial period of oxygen depletion and just after the disappearance of anoxia, while they diminished in the anoxic hypolimnion by midsummer. The seasonal behavior of trivalent methylarsenicals, which are readily oxidized in oxic environments, was similar to that of DMAA(V). The total arsenic concentration in the surface layer rose to a maximum in late summer. Methylarsenicals did not increase in such a way that the total arsenic concentration increased during summer. © 1997 by John Wiley & Sons, Ltd.     

Changes in density and surface tension of water in silica pores

 The density and surface tension of water in small pores of silicas have been investigated. These physical properties of water in the pores were calculated from a comparison of pore volumes and pore radii which were estimated from adsorption and desorption isotherms of nitrogen and water. Below a pore radius of about 5 nm both the density and the surface tension of water in the pores were smaller than those of the bulk liquid and decreased with a decrease in pore size. The density of water in the pores decreased with an increase in the concentration of surface hydroxyl groups. Similarly the surface tension of water in the pores is influenced by the surface hydroxyl groups. Anomalous changes in the density and surface tension of the water in the pores are attributed to the interaction of water molecules with surface hydroxyl groups and hydrogen-bond formation among water molecules. Received: 20 April 1999 Accepted in revised form: 17 November 1999     

Radial structure and property relationship in the thermal stabilization of PAN precursor fibres

Here we report on the role of oxygen in the evolution of radial heterogeneity in the fibre structure and properties of PAN fibres stabilized in air and vacuum at different temperatures. Modulus mapping by Nano-indentation showed heterogeneous modulus distribution in the fibres treated in air, while no variation in modulus was observed in fibres processed in vacuum. Raman spectroscopy and elemental analysis revealed that the temperature dependent oxygen diffusion from skin to core of the fibres assisted in the evolution of higher extent of sp²-hybridized carbons in the skin compared to core of the air treated samples. Conversely, no radial structure variations were observed in the vacuum treated fibres. Higher modulus in the skin of air-treated fibres was due to the formation of compact structures which was associated with the enhanced intermolecular interactions facilitated by the formation of C=C bonds within the polymer backbone, promoted by oxidative-dehydrogenation reaction. Supporting these observations, the fracture morphology examined by SEM showed a brittle fracture in the skin and ductile fracture in the core.     

Analysis of sequence repeats of proteins in the PDB

Internal repeats in protein sequences play a significant role in the evolution of protein structure and function. Applications of different bioinformatics tools help in the identification and characterization of these repeats. In the present study, we analyzed sequence repeats in a non-redundant set of proteins available in the Protein Data Bank (PDB). We used RADAR for detecting internal repeats in a protein, PDBeFOLD for assessing structural similarity, PDBsum for finding functional involvement and Pfam for domain assignment of the repeats in a protein. Through the analysis of sequence repeats, we found that identity of the sequence repeats falls in the range of 20–40% and, the superimposed structures of the most of the sequence repeats maintain similar overall folding. Analysis sequence repeats at the functional level reveals that most of the sequence repeats are involved in the function of the protein through functionally involved residues in the repeat regions. We also found that sequence repeats in single and two domain proteins often contained conserved sequence motifs for the function of the domain.     

Topical Problems in Elemental Analysis of Advanced Ceramic Materials

Selected prominent problems in the analysis of advanced ceramic materials are surveyed. The importance of reliability of results is discussed in the field of elemental trace- and microanalysis in view of its interaction with economy, power of detection, local resolution and speciation selectivity. Particular problems in the analysis of major constituents, trace components and microlocal distributions are based on the striking propertics of ceramics; they are exemplified. Analytical assistance must start from the beginning of the production processing, in the preparation of the powdered base materials. Determination of the stoichiometry requires high accuracy and differentiation of chemical species in bulk and surface analysis of ceramic base powders. Element trace determination by direct instrumental methods requires standard reference materials for calibration; these are currently inavailable in a sufficient variety. For optimum reliability and power of detection, element traces must be prepared in isolated form in a small excitation volume for analysis. A review on the state-of-the-art of wet-chemical combined procedures is presented. Decomposition position procedures are emphasized, due to their risk of contributing severe systematic error. Combustion in elementary fluorine is presented for decomposition of refractory materials. The performance of some direct procedures is discussed. Very efficient methods are available for element trace determinations in ceramic materials, offering high detection power. Several approaches for high-resolution local microanalysis in non-conductive ceramic materials are identified as the most promising development in the analysis of sintered compact ceramic products and devices.     

Phosphaalkynes—Syntheses,Reactions, Coordination Behavior [New Synthetic Methods (73)]

Organophosphorus compounds have been applied in two ways in chemical synthesis. They can either be used as a reagent in a step of the synthesis (for example, in the Wittig reaction) or they can be incorporated directly into the target molecule. This second application, in particular, has expanded greatly in the last few years with the preparation of low-coordination phosphorus compounds. These include the phosphaalkynes, which are of great interest to organic and inorganic chemists. Phosphaalkynes have been employed in the synthesis of heterocyclic compounds, phosphaarenes and their valence isomers, and polycyclic compounds. Further applications have been the use of phosphaalkynes as new ligand systems in complex chemistry and their cyclooligomerization with organometallic reagents. While the chemical properties of phosphaalkynes have little in common with those of nitriles, they are in many ways very similar to those of the isoelectronic acetylenes.     

LD-2复合缓蚀剂对海水介质混凝土中钢筋阻锈作用研究

利用电化学检测技术和海水浸泡试验等方法 ,观测和研究了经筛选研制的LD_2复合缓蚀剂对海水介质中钢筋腐蚀电化学行为的影响 ,考察和评价了复合缓蚀剂对钢筋的阻锈作用 .结果表明 ,LD_2复合缓蚀剂主要起阳极型缓蚀剂作用 .在海水中加入 2 5 g·L- 1复合缓蚀剂后 ,钢筋的腐蚀电位提高约 0 .2 2 0V ,腐蚀电流降低至未加缓蚀剂的 1% ,缓蚀效率达 99% .钢筋混凝土试样在海水中浸泡 2年 ,表明混凝土中加入占水泥重量 1.0 %～ 2 .5 %LD_2复合缓蚀剂时 ,能有效阻止混凝土中钢筋的腐蚀     

Calibration methods for microdialysis sampling in vivo: muscle and adipose tissue

Calibration methods for microdialysis sampling were studied in the muscle and adipose tissue of rats. Both the delivery method and the no-net-flux method were used to determine the extraction efficiency (EE) of acetaminophen and caffeine in both tissues. There was no concentration dependence of the EE either in vitro or in vivo for either acetaminophen or caffeine. The EEs determined by the delivery and no-net-flux methods were not different. However, the EEs of both caffeine and acetaminophen determined in vitro were significantly higher than those determined in the muscle and adipose. This indicates that mass transfer in the tissue is the rate-determining factor for the EE in vivo. The relative difference between the EE in vitro and the EE in the muscle was smaller than the difference between the EE in vitro and the EE in the adipose. In addition, the EE in the muscle decreased more than the EE in the adipose after the animal was euthanized. This indicated that exchange between the extracellular fluid and plasma is the rate-determining step in mass transport relative to microdialysis sampling. This has a more significant effect on the EE in the muscle than the EE in the adipose. Both the delivery and no-net-flux methods can be used to calibrate microdialysis probes in the muscle and adipose.     

Effect of pulp composition on the characteristics of residuals in CMC made from such pulps

Four different spruce sulphite pulp samples were used for the preparation of carboxymethylcellulose (CMC). The characteristics of the unreacted fibre and particle residuals obtained in the CMC-preparation were used to establish a correlation between the hemicellulose in the pulp and the intrinsic viscosity, i.e.,␣cellulose chain length and the occurence of unreacted residuals. It was shown that the residual particles in the CMC consisted of fibres, fibre fractions and gel particles of different degrees of substitution. The results suggested that pulps with long cellulose chains, i.e., pulps with high intrinsic viscosities, resulted in particles that were more substituted and more swollen. These pulps also resulted in more substituted hemicelluloses in the CMC and more substituted residuals. It was also suggested that galactoglucomannan in the cellulose pulps is favourable for the swelling which results in more substituted hemicelluloses in the CMC and more swollen residuals. The amount of residuals was influenced mainly by the characteristics of the cellulose in the pulp. It is therefore believed that a combination of high viscosity and a suitable combination of hemicelluloses is the most favourable way of eliminating the occurrence of undissolved residuals in CMC.     

Platinum levels in urban soils from Palermo (Italy); Analytical method using voltammetry

A fast accumulation of platinum in the environmental and biological matrices was observed in the last years and concern arose about potential environmental and health risks.The toxicity of platinum species has been investigated in various studies, some of their, especially the chlorinated ones, are very toxic and allergenic. Information of the acute toxicity of some Pt-chlorinated salts and evidence of DNA damage due to Pt exposure have been observed both in vitro and in vivo.Taking into account what is written above, the development of reliable analytic methods to measure very low Pt concentrations is required. In this work was developed a reliable method for the determination of Pt in soils because of inherent difficulties in using conventional techniques, in particular, the ICP-OES technique. A determination of Pt using ICP-MS, for instance, is problematic, due to interfering signals. Differential pulse voltammetry (DPV/a) was employed by us for the determination of platinum in soils collected in Palermo area. Possible interferences by other environmental metals have been also evaluated.All samples show concentrations of Pt above average upper crust values; concentrations were found in the ranges 0.6–2240 μ/kg d.w. We carried out linear regression analysis between total Pt concentrations in soils obtained in this work and Pt concentrations in leaves of Nerium oleander measured in previous researches. The high correlation coefficient obtained confirms the geographical distribution of the considered pollutant in the Palermo area.     

The transport properties of polyimide isomers containing hexafluoroisopropylidene in the diamine residue

The effect of modification of the central moiety of the dianhydride residue and isomerism on the gas transport and physical properties were compared for six polyimides containing the hexafluoroisopropylidene group in the diamine residue. Substitution of bulkier groups within the dianhydride residue resulted in disruption of chain packing and slight increases in resistance to chain motions which led to an increase in permeability with little loss in selectivity. The permeabilities and diffusivities in the meta connected polyimide isomers were considerably lower than in the para connected polyimide isomers. Similarly, the permselectivities in the meta connected isomers were consistently higher than in the para connected isomers. These lower permeabilities and higher permselectivities were a result of the more dense packing and a significant suppression of small scale motions in the meta connected isomers. The suppression of segmental mobility in the meta connected isomers was indicated by an increase in the sub Tg transition temperatures in these materials relative to the para connected isomers. The differences in transport properties for these polyimides were attributed to contributions by several factors, including: (1) total free volume (2) distribution of free volume (3) intersegmental resistance to chain motions, and (4) intrasegmental resistance to chain motions. © 1994 John Wiley & Sons, Inc.     

The Effect of Antiretroviral Therapy on SIRT1, SIRT3 and SIRT6 Expression in HIV-Infected Patients

Human Immunodeficiency Virus (HIV) infection and the chronic use of combined antiretroviral therapy (cART) may affect the occurrence of certain disturbances in the body. There is growing interest in sirtuins–enzymes involved in the regulation of many metabolic processes in the organism and in the pathogenesis of many diseases which also exhibit potential antiviral activity. The aim of the study was to investigate the connection of cART to the expression of Sirtuin 1 (SIRT1), Sirtuin 3 (SIRT3) and Sirtuin 6 (SIRT6) in HIV-infected men. The plasma levels of sirtuins were measured before and one year after cART, and related to HIV viral load, lymphocytes T CD4+ and CD8+ count as well as the applied cART. The levels of sirtuins in plasma were measured in HIV-infected patients (n = 53) and the control group (n = 35) by immunoassay methods. There were statistically significant (p < 0.05) differences between SIRT6 in the HIV-infected patients before therapy and in the subgroups, depending on the count of lymphocytes T CD8+. There were significant differences in the levels of SIRT1 depending on the applied treatment regimen. The obtained results indicate the most significant changes in the expression of SIRT6 in the course of HIV infection and suggest an influence of the type of cART on the level of SIRT1, which indicates its important role in the course of HIV.     

UNDERSTANDING THE HYDROPHOBIC EFFECT

The hydrophobic effect is the common expression for processes where nonpolar groups in molecules are spontaneously removed from water. Thermodynamic analysis of hydrocarbon solubility in water, micellization and adsorption of surfactants show that the hydrophobic effect can be understood in terms of two contributions. The first contribution is attributed to the structuring, or rearrangement, of water molecules in the vicinity of a hydrophobe. This contribution is favorable, and hence increases the solubility of hydrocarbons in water, increases the cmc, and decreases the adsorption of surfactants. The second contribution is attributed to the formation of a cavity in the water in order to accomodate the hydrophobe. This contribution dominates over the first one and is unfavorable, i.e. it decreases the solubility of hydrocarbons in water, decreases the cmc, and increases the adsorption of surfactants. Thus, the cause of the hydrophobic effect is to be found in the large energy required to form a cavity in the water. On the other hand the temperature dependence of the hydrophobic effect is entirely determined by the water structuring, or rearrangement, in the vicinity of a hydrophobe.