Determination of stavudine in human serum by on-line solid-phase extraction coupled to high-performance liquid chromatography with electrospray ionization tandem mass spectrometry: application to a bioequivalence study

A method based on solid-phase extraction (SPE) coupled to high-performance liquid chromatography (HPLC) with positive ion electrospray ionization tandem mass spectrometry (ESI-MS/MS) detection was developed for the determination of stavudine in human serum, using didanosine as internal standard. The acquisition was performed in multiple reaction monitoring (MRM) mode. The method was linear over the studied range (10-2000 ng/mL), with r(2) > 0.99, and the run time was 4 min. The intra- and inter-assay precisions (%) were in the ranges 0.1-13.6 and 2.6-9.9, respectively, and the intra- and inter-assay accuracies were >92%. The absolute recoveries were approximately 100% (10 ng/mL), 98% (30 ng/mL), 105% (750 ng/mL) and 105% (1500 ng/mL). The limits of detection and quantitation were 4 and 10 ng/mL, respectively. The analytical method was applied to a bioequivalence study, in which 24 healthy adult volunteers (12 men) received single oral doses (40 mg) of reference and two test stavudine formulations, in an open, three-period, randomized, crossover protocol. The 90% confidence interval of the individual ratios (test formulation/reference formulation) for C(max) (peak serum concentration), AUC(0-10) and AUC(0-inf) (areas under the serum concentration vs. time curve from time zero to 10 h and to infinity, respectively), were in the range 80-125%, which supports the conclusion that the two test formulations are bioequivalent to the reference formulation with respect to the rate and extent of stavudine absorption.     

Synthesis of ORMOSIL silica/rhodamine 6G: Powders and compacts

The sol-gel method was used to prepare a silica matrix with rhodamine 6G. This dye was chemically bonded to silica matrix by grafting reactions, obtaining ORMOSIL/R6G powder, at two different concentrations, 0.03 mmol of dye/g silica and 0.009 mmol of dye/g silica, called ORMOSIL1 and ORMOSIL2, respectively. Fluorescent compacts were also obtained, through the high-pressure processing of these powders, at 7.7 GPa and room temperature. The microstructure, chemical composition and thermal stability of the powders and compacts were comparatively studied, by N₂ adsorption/desorption isotherms, FTIR spectroscopy, thermogravimetric analyses (TGA) and elemental analyses for carbon, hydrogen, and nitrogen (CHN). The optical behavior was studied by fluorescence spectroscopy. The ORMOSIL1 compacts were completely opaque showing that the compaction was not effective, due to the high organic grade incorporated into the starting ORMOSIL1 powder. The ORMOSIL2 compacts were transparent showing an effective compaction, which are in agreement to the great surface area and porosity reduction. Additionally, it was observed in TGA results, the retention of the organics in these samples up to temperatures near 300 °C. The fluorescence emission showed that the dye was dispersed in molecular level in all samples.     

A new genosensor for meningococcal meningitis diagnosis using biological samples

In this work, a new electrochemical biosensor for DNA detection of bacterial meningitis is proposed. The system is based on specific DNA fragments from the Neisseria meningitidis genome as a probe incorporated on graphite electrodes modified with poly(4-aminophenol). Detection of a complementary oligonucleotide sequence, a specific 710-base pair amplicon, and the genomic DNA of bacteria was carried out by differential pulse voltammetry, using ethidium bromide as an electroactive indicator of hybridization. The complementary oligonucleotide and the genomic DNA of Neisseria meningitidis were quantified by the genosensor, showing detection limits of 0.6 ng μL^?1 and about 6 ng μL^?1, respectively. Morphological differences were observed between hybridized and unhybridized surfaces by atomic force microscopy. The biosensor showed high selectivity, discriminating non-specific targets, and high stability retaining over 98% of its original activity after 120 days of storage. The bioelectrode was effective in discriminating the genomic DNA in samples with human serum without significant interference, proving to be an interesting platform for meningococcal meningitis diagnosis.     

In-water reactivity of nucleosides and nucleotides: one-step preparation and biological evaluation of novel ferrocenyl-derivatives

The reactivity in water of a series of nucleosides and nucleotides towards ferrocenemethanol was investigated. Several adducts incorporating the ferrocenemethyl moiety into the heterocyclic base were isolated and their activity was tested against HIV-1, HBV, YFV, BVDV and several bacteria. However, none of the new compounds showed significant antiviral activity nor cytotoxicity. The reaction with ferrocenemethanol of the model dinucleotide ^5′dCpdG^3′, for a direct comparison of the behaviour of purine versus pyrimidine bases, is also discussed.     

Effect of dye aggregation on triarylmethane-mediated photoinduced damage of hexokinase and DNA

The observation that enhanced mitochondrial membrane potential is a prevalent cancer cell phenotype has provided the conceptual basis for the development of mitochondrial targeting as a novel therapeutic strategy for both chemo- and photochemotherapy of neoplastic diseases. Cationic triarylmethane (TAM(+)) dyes represent a series of photosensitizers whose phototoxic effects develop at least in part at the mitochondrial level. In this report we describe how the molecular structure of four representative TAM(+) dyes (Crystal Violet, Ethyl Violet, Victoria blue R, and Victoria pure blue BO) affects their efficiency as mediators of the photoinduced inactivation of two model mitochondrial targets, hexokinase (HK) and DNA. Our results have indicated that TAM(+) dyes efficiently bind to HK and DNA in aqueous media both as dye monomers and aggregates, with the degree of aggregation increasing with increasing the lipophilic character of the photosensitizer. The efficiency with which HK and DNA are damaged upon 532 nm photolysis of biopolymer-TAM(+) complexes was found to decrease upon increasing the degree of dye aggregation over these macromolecular templates. Comparative experiments carried out both in water and in D(2)O, and in air-equilibrated and nitrogen-purged samples have also indicated that, at least when Crystal Violet is used as the photosensitizer, the mechanism of macromolecular damage does not require the involvement of molecular oxygen to operate. This finding makes Crystal Violet a potential candidate for use in photochemotherapy of hypoxic or poorly perfused tumor areas.     

Processing, characterization and properties of conducting polyaniline-sulfonated SEBS block copolymers

Incorporation of polyaniline (PAni) into thermoplastic elastomers can be used to produce materials that potentially combine the good mechanical properties and processability of thermoplastic elastomers with electrical, magnetic and optical characteristics of PAni. In this work, a polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene copolymer (SEBS) was chemically modified by grafting a sulfonic group onto the chain backbone in order to promote higher levels of compatibility between the thermoplastic elastomer and polyaniline. The sulfonation process was performed by reacting SEBS with acetyl sulfate. Infrared spectroscopy and titration were used to monitor the amount of sulfonic groups successfully grafted on SEBS. Mechanical tests performed in sulfonated SEBS showed that sulfonation levels lower than 15% did not reduce substantially the mechanical properties of SEBS. PAni doped with dodecylbenzenesulfonic acid (PAni·DBSA), used in the preparation of the blends, was prepared by the “in situ doping polymerization” method. PAni·DBSA was then blended in solution with SEBS having different levels of sulfonation. The introduction of sulfonic group into the structure of SEBS improved coulombic interactions between the phases in the blend and enhanced compatibility. As a consequence, higher values of electrical conductivity (measured by the four-probe method) were achieved in blends with sulfonic groups grafted onto polymer chains. Concentrations as low as 20 wt% of PAni were able to lead to electrical conductivities of PAni·DBSA/sulfonated SEBS blends close to 1.2 S/cm. Optical micrographs of the blends showed that PAni·DBSA/sulfonated SEBS microstructure is composed of a very disperse group of small conducting particles. This type of microstructure would then be responsible for the enhanced electrical conductivity and low percolation threshold of PAni·DBSA/sulfonated SEBS, when compared to PAni·DBSA/SEBS blends.     

All electron fully relativistic Dirac–Fock calculation for darmstadtium carbide using prolapse free basis set

For the first time, ab inito all electron fully relativistic and correlated Dirac–Fock calculations with prolapse free basis set are reported for a Super Heavy Element. We investigated the relativistic effects on bonding and on some spectroscopic constants for the darmstadtium carbide and our results at DF/CCSD(T) with a prolapse free basis set suggest for R_e, ω_e and D_e the values of 174 pm, 1114 cm⁻¹ and 7.29 eV, respectively. These values are very similar to the values for PtC found on literature. It was also found that prolapse free basis set may be important to estimate the dissociation energy using Relativistic 4-components correlated methods.     

Free products of abelian groups in the unit group of integral group rings

We classify finite groups which are such that the unit group of the integral group ring has a subgroup of finite index which is a non-trivial free product of abelian groups.

     

Ionophilic phosphines: versatile ligands for ionic liquid biphasic catalysis

Phosphine ligands bearing an imidazolium fragment were easily prepared by one-step radical chain addition of secondary phosphines to allyl or vinyl imidazolium salts. These ligands were used to prepare new ionophilic second generation Grubbs-type catalysts. The catalyst immobilized in 1-butyl-3-methyl imidazolium ILs shows good catalytic activity in RCM reactions of several substrates and, depending on the media employed, is stable up to eight cycles.     

Monoterpenes and Sesquiterpenes of Essential Oils from Psidium Species and Their Biological Properties

Psidium (Myrtaceae) comprises approximately 266 species, distributed in tropical and subtropical regions of the world. Psidium taxa have great ecological, economic, and medicinal relevance due to their essential oils’ chemical diversity and biological potential. This review reports 18 Psidium species growing around the world and the chemical and biological properties of their essential oils. Chemically, 110 oil records are reported with significant variability of volatile constituents, according to their seasonality and collection sites. Monoterpenes and sesquiterpenes with acyclic (C₁₀ and C₁₅), p-menthane, pinane, bisabolane, germacrane, caryophyllane, cadinane, and aromadendrane skeleton-types, were the primary constituents. The essential oils showed various biological activities, including antioxidant, antifungal, antibacterial, phytotoxic, larvicidal, anti-inflammatory, and cytotoxic properties. This review contributes to the Psidium species rational and economic exploration as natural sources to produce new drugs.