Purity determination of a new antifungal drug candidate using quantitative 1H NMR spectroscopy: Method validation and comparison of calibration approaches

Quantitative nuclear magnetic resonance (qNMR) is an analytical technique that offers numerous advantages in pharmaceutical applications including minimum sample preparation and rapid data collection times with no need for response factor corrections, being a powerful tool for assaying drug content in both drug discovery and early drug development. In the present work, we have applied qNMR, using both the internal standard and the electronic reference to access in vivo concentrations 2 calibration methods, to assess the purity of RI76, a novel antifungal drug candidate. NMR acquisition and processing parameters were optimized in order to obtain spectra with intense, well-resolved signals of completely relaxed nuclei. The analytical method was validated following current guidelines, demonstrating selectivity, linearity, accuracy, precision, and robustness. The calibration approaches were statistically compared, and no significant difference was observed when comparing the obtained results and their dispersion in terms of relative standard deviation. The proposed qNMR method may, therefore, be used for both qualitative and quantitative assessments of RI76 in early drug development and for characterization of this compound.     

Low-background,digital gamma-ray spectrometer with BEGe detector and active shield: commissioning,optimisation and software development

Journal of Radioanalytical and Nuclear Chemistry - This paper presents results of the development process of low-background, digital gamma-rays spectrometer equipped with Broad Energy Germanium...     

The Double Face of Ketamine—The Possibility of Its Identification in Blood and Beverages

The purpose of this study was to develop and validate a high-sensitivity methodology for identifying one of the most used drugs—ketamine. Ketamine is used medicinally to treat depression, alcoholism, and heroin addiction. Moreover, ketamine is the main ingredient used in so-called “date-rape” pills (DRP). This study presents a novel methodology for the simultaneous determination of ketamine based on the Dried Blood Spot (DBS) method, in combination with capillary electrophoresis coupled with a mass spectrometer (CE-TOF-MS). Then, 6-mm circles were punched out from DBS collected on Whatman DMPK-C paper and extracted using microwave-assisted extraction (MAE). The assay was linear in the range of 25–300 ng/mL. Values of limits of detection (LOD = 6.0 ng/mL) and quantification (LOQ = 19.8 ng/mL) were determined based on the signal to noise ratio. Intra-day precision at each determined concentration level was in the range of 6.1–11.1%, and inter-day between 7.9–13.1%. The obtained precision was under 15.0% (for medium and high concentrations) and lower than 20.0% (for low concentrations), which are in accordance with acceptance criteria. Therefore, the DBS/MAE/CE-TOF-MS method was successfully checked for analysis of ketamine in matrices other than blood, i.e., rose wine and orange juice. Moreover, it is possible to identify ketamine in the presence of flunitrazepam, which is the other most popular ingredient used in DRP. Based on this information, the selectivity of the proposed methodology for identifying ketamine in the presence of other components of rape pills was checked.     

Mechanism of Iodine(III)-Promoted Oxidative Dearomatizing Hydroxylation of Phenols: Evidence for a Radical-Chain Pathway

The oxidative dearomatization of phenols with the addition of nucleophiles to the aromatic ring induced by hypervalent iodine(III) reagents and catalysts has emerged as a highly useful synthetic approach. However, experimental mechanistic studies of this important process have been extremely scarce. In this report, we describe systematic investigations of the dearomatizing hydroxylation of phenols using an array of experimental techniques. Kinetics, EPR spectroscopy, and reactions with radical probes demonstrate that the transformation proceeds by a radical-chain mechanism, with a phenoxyl radical being the key chain-carrying intermediate. Moreover, UV and NMR spectroscopy, high-resolution mass spectrometry, and cyclic voltammetry show that before reacting with the phenoxyl radical, the water molecule becomes activated by the interaction with the iodine(III) center, causing the Umpolung of this formally nucleophilic substrate. The radical-chain mechanism allows the rationalization of all existing observations regarding the iodine(III)-promoted oxidative dearomatization of phenols.     

Effect of pozzolanic waste materials on hydration peculiarities of Portland cement and granulated expanded glass-based plaster

Journal of Thermal Analysis and Calorimetry - The article analyses the peculiarities of the combined effect on hydration process of the following pozzolanic additives: metakaolin waste (MW),...     

Effect of milled fluidised bed cracking catalyst waste on hydration of calcium aluminate cement and formation of binder structure

The effect of Bi addition on precipitation and dissolution, in Cu–9at% In and Cu–5at% Sb supersaturated solid solutions, has been studied by several complementary techniques. Differential Dilatometry and Differential Scanning Calorimetry permit only the analysis of the δ phase dissolution kinetic in sufficiently aged samples. Delayed spheroidization due to Bi segregation around the precipitated lamellae, observed by Transmission Electron Microscopies in the first alloy, gives a residual interfacial energy leading to accelerated δ phase dissolution with decreased activation energy. Kinetics parameters evolution indicates a progressive δ phase continuous dissolution which makes available a small chemical driving force at high temperatures and leads to an increasing activation energy during dissolution. However, Bi dispersed particles in the second alloy haven’t effect on the dissolution but they cause a contraction above 833 K. Kinetics parameters evolution indicates rapid δ phase dissolution that shifted to high temperatures where an important chemical driving force for solution treatment is available. It leads to almost constant activation energy.

     

Evaluation of gamma irradiation effect on physico-chemical properties of a mixed beverage based in soy milk and grape juice

The effects of the main operation variables on the electrochemical oxidation of simulated tributyl phosphate (TBP) waste by a boron-doped diamond anode are individually studied. The optimum operating conditions are obtained as follows: 4 g L^?1 initial TBP concentration, 180 min degradation time, 40 mA cm^?2 current density, 0.5 mol L^?1 Na₂SO₄ as the supporting electrolyte, and unadjusted pH of the aqueous phase. Under such conditions, a chemical oxygen demand (COD) removal ratio of 82.3% is achieved, and the energy consumption is 26.16 kWh m^?3. A degradation mechanism of TBP is tentatively proposed.