Enantioselective analysis of venlafaxine and its active metabolites: A review on the separation methodologies

Venlafaxine (VFX) is a serotonin and norepinephrine reuptake inhibitor chiral drug used in therapy as an antidepressant in the form of a racemate consisting of R‐ and S‐VFX. The two enantiomers of VFX exhibit different pharmacological activities: R‐VFX inhibits both norepinephrine and serotonin synaptic reuptake, whereas S‐VFX inhibits only the serotonin one. R‐ and S‐VFX are metabolized in the liver to the respective R‐ and S‐O‐desmethylvenlafaxine (ODVFX), R‐ and S‐N‐desmethylvenlafaxine (NDVFX), and R‐ and S‐N,O‐didesmethylvenlafaxine (NODVFX). The pharmacological profile of ODVFX is close to that of VFX, whereas the other two chiral metabolites (NDVFX and NODVFX) have lower affinity for the receptor sites. The pharmacokinetics of the VFX enantiomers appear stereoselective, including the metabolism process. In the past 20 years, several studies describing the enantioselective analysis of R‐ and S‐VFX in pharmaceutical formulations and its chiral metabolites in biological matrices were published. These methods encompass liquid chromatography coupled with UV detection, mass spectrometry, or tandem mass spectrometry, and capillary electrophoresis. This paper reviews the published methods used for the determination of the individual enantiomers of VFX and its chiral metabolites in different matrices.     

Plasmon heating mediated Friedel-Crafts alkylation of anisole using supported AuNP@Nb2O5 catalysts

Two different hybrid materials composed of gold nanoparticles (AuNPs) supported on either commercial niobium oxide HY 340 or mesoporous niobium oxide catalyzed the Friedel-Crafts alkylation of anisole by benzyl chloride. Excitation of the surface plasmon of the supported AuNPs allowed the reaction to occur at lower temperatures by acting as an alternative heat source. The localized heating produced via plasmon excitation permitted the acid catalyzed reaction to occur - at the Lewis acid sites on the Nb₂O₅ support - at 80 °C while thermal-dark reactions using a conventional heat source, required temperatures of 120 °C or higher. The catalytic activity of the tested hybrid materials decreased with storage time. However, the deactivation showed to be reversible upon lyophilisation indicating that the nature of the deactivation could be due to water adsorption.     

Epoxides related to dioncoquinone B: Synthesis,activity against multiple myeloma cells,and search for the target protein

Epoxide 2b is an analog of the synthetic intermediate 2a en route to the polyketide-derived antitumoral naphthoquinone dioncoquinone B (1), isolated from cell cultures of the tropical liana Triphyophyllum peltatum (Dioncophyllaceae). Compound 2b was found to induce strong apoptosis in multiple myeloma cells at a concentration (EC₅₀?=?3.5?μM), distinctly lower than that of 1 and any related analog, without exerting significant toxicity against normal blood cells. Preliminary studies showed that 2b follows different SAR rules as compared to the naphthoquinones. Among the series of synthesized epoxides, 2b was the most active one and was thus, after biotinylation, subjected to mass spectrometry-based affinity capture experiments aiming at the identification of target proteins. The MS data revealed 2b to address proteins that are associated with stress regulation processes which are critical for multiple myeloma cell survival.     

Effect of Cold Atmospheric Pressure Plasma on Maize Seeds: Enhancement of Seedlings Growth and Surface Microorganisms Inactivation

Cold atmospheric pressure ambient air plasma generated by Diffuse Coplanar Surface Barrier Discharge (DCSBD) was investigated for inhibition of native microbiota and potentially dangerous pathogens (Aspergillus flavus, Alternaria alternata and Fusarium culmorum) on the maize surface. Moreover, the improvement of germination and growth parameters of maize seeds was evaluated. Maize (Zea mays L.; cv. Ronaldinio), one of the most important cultivated crops worldwide, was selected as the research material. Electrical measurements confirmed the high volume power density (80 W cm^?3) of DCSBD plasma. Non-equilibrium plasma state evaluated using optical emission spectroscopy showed values of vibrational and rotational temperature (2700?±?300) K and (370?±?75) K, respectively. Changes on the plasma treated seeds surface were studied by water contact angle measurement, scanning electron microscope analysis and Fourier transform infrared spectroscopy. A complete devitalisation of native microbiota on the surface of seeds was observed after a short treatment time of 60 s (bacteria) and 180 s (filamentous fungi). The plasma treatment efficiency of artificially contaminated maize seeds was estimated as a reduction of 3.79 log (CFU/g) in F. culmorum after a 60-s plasma treatment, 4.21 log (CFU/g) in A. flavus and 3.22 log (CFU/g) in A. alternata after a 300-s plasma treatment. Moreover, the obtained results show an increase in wettability, resulting in a better water uptake and in an enhancement of growth parameters. The investigated DCSBD plasma source provides significant technical advantages and application potential for seed surface finishing without the use of hazardous chemicals.     

A Jocic-type approach for a practical and scalable synthesis of pyrrolonaphthoxazepine (PNOX)-based potent proapoptotic agents

We developed a Jocic-type protocol for the construction of the pyrrolonaphthoxazepine (PNOX) core. After an initial investigation based on the isolation of a trichloromethyl carbinol derivative, we shifted our attention towards a multicomponent single-step protocol. Screening of a variety of bases and solvents led to the identification of the optimum conditions for the preparation of the key α-aryloxy carboxylic acids to undergo intramolecular cyclization. The novel chemical route significantly improved overall yields for the preparation of PNOX-based compounds and was successfully extended to the preparation of 1,4-benzoxazinone-based templates.     

Sol-gel synthesis of ZnO/Zn<Subscript>2-x</Subscript>Fe<Subscript>x</Subscript>TiO<Subscript>4</Subscript> powders: structural properties,electrical conductivity and dielectric behavior

The aim of this work was an investigation of structural and electrical properties of ZnO/Zn_2-xFe_xTiO₄ (x?=?0.7, 1, 1.4) powders. The compounds obtained by sol-gel method are characterized by several techniques: X-ray diffraction (XRD), N₂ adsorption–desorption isotherms, scanning and transmission electron microscopy (SEM and TEM), X-ray photoelectron spectroscopy (XPS), electrical and dielectrical measurements. The XRD, SEM and XPS analysis confirmed the formation of ZnFeTiO₄ inverse spinel structure. The electrical and dielectrical properties of ZnO/Zn_2-xFe_xTiO₄ (x?=?0.7, 1, 1.4) were measured by impedance spectroscopy, revealing a decrease in the electrical conductivity and the dielectric constant with Fe content.

Open image in new window

     

Elemental Analysis of Phytotherapeutic Products by Inductively Coupled Plasma–Tandem Mass Spectrometry

A procedure for the determination of As, Cd, Cr, Ni, Pb, and V in phytotherapy medicines by inductively coupled plasma–tandem mass spectrometry is reported. The use of tandem mass spectrometry with oxygen into an octopole reaction system at various gas flow rates and the combination of on-mass and mass-shift modes was evaluated. Cadmium, Cr, Ni, and Pb were determined as free atomic ions while As and V were determined as the oxides AsO⁺ and VO⁺ in the same run. Samples were prepared by microwave-assisted digestion with dilute nitric acid and hydrogen peroxide. Two plant-certified reference materials (apple leaves and tomato leaves) were used to check the accuracy. For tandem mass spectrometry with 0.5?mL min^?1 O₂, recoveries in the 85–113% were typically obtained and no statistical differences were observed at the 95% confidence level (t-test) in comparison with the certified values. Using these conditions, the limits of detection for the method were 0.01, 0.0002, 0.008, 0.008, 0.003, and 0.002?µg g^?1 for As, Cd, Cr, Ni, Pb, and V, respectively. The procedure was used for the analysis of four phytotherapic drugs and the determined concentrations were up to 0.168?µg g^?1 As, 0.03?µg g^?1 Cd, 0.82?µg g^?1 Cr, 1.18?µg g^?1 Ni, 0.52?µg g^?1 Pb, and 2.4?µg g^?1 V with average precision values of 8% as the relative standard deviation. The found concentrations were compared with limits proposed in official guidelines and, in most cases, the values were below the maximum limits allowed.