Simultaneous measurement of drug metabolic stability and identification of metabolites using ion-trap mass spectrometry

The use of in vitro drug metabolism data in the understanding of in vivo pharmacokinetic, safety and toxicity data has become a large area of scientific interest. This has stemmed from a trend in the pharmaceutical industry to use in vitro data generated from human tissue as a criterion to select compounds for further investigation. As well as measuring metabolic stability in vitro using human liver microsomal preparations, the identification of possible metabolite(s) formed may play a vital role in Hit-to-Lead and Lead optimisation processes. The data-dependent scan function mode with the ion-trap instrumentation provides the ability to measure the metabolic stability and identification of possible metabolites of a compound. A gradient liquid chromatographic method with a run time of 6 min/injection was developed for this purpose. The approach of simultaneous metabolic stability measurements and rapid identification of metabolites of drugs with high (verapamil), medium (propranolol and cisapride) and low (flunarazine) metabolic stabilities using ion-trap mass spectrometry is described. The metabolites identified after 15 min incubation for verapamil, propranolol and cisapride are in good agreement with those reported as the major metabolites in human in vivo studies.     

Electrocatalytic Reduction of Oxygen at Glassy Carbon Electrodes Coated with Diazonium‐derived Porphyrin/Metalloporphyrin Films

In this study, the influence of the film structure was investigated on the electrocatalytic oxygen reduction at GC electrodes covered with porphyrin and metalloporphyrin rings via the diazonium modification method. For that purpose, primarily, tetraphenylporphyrin (TPP) films on GC electrode surfaces were prepared by electroreduction of in situ generated diazonium salts of 5‐(4‐aminophenyl)‐10,15,20‐triphenylporphyrin (APP) and 5,10,15,20‐tetrakis(4‐aminophenyl)porphyrin (TAPP) molecules. Next, the formation of metalloporphyrin films on the modified surfaces was accomplished through the complexation reactions of surface porphyrin rings with metal ions in the salt solutions containing Mn(II), Fe(III) and Co(II) ions. The resulting porphyrin and metalloporphyrin layers were identified with XPS and ICP‐MS. The electrochemical barrier properties of the films on GC surfaces were examined by cyclic voltammetry in K₃Fe(CN)₆ aqueous solution. The electrocatalytic abilities of the resulting films were also investigated for the oxygen electrochemical reduction by employing cyclic voltammetry in PBS solutions saturated with oxygen. The results showed that the oxygen reduction potentials on modified GC electrodes were shifted to less negative potentials compared to that of bare GC electrode. Also, it was obtained that the oxygen reduction reaction was more effective on the GC electrodes modified with TPP rings by using TAPP molecules than those prepared by using APP molecules.     

Optical properties of methanol at high pressures

The pressure dependence of the refractive index of methanol has been measured in a diamond-anvil cell up to 5·6 GPa at room temperature. These experiments cover the liquid phase of methanol (below 3·6 GPa) as well as the ‘superpressed fluid’ phase above 3·6 GPa. We have extracted the polarizability of methanol from our experimental data and the equation of state by using the Lorentz-Lorenz equation.     

Thermoresponsive oligo(ethylene glycol) methacrylate colloids with antifouling surface properties

Thermoresponsive polymeric colloids attract great attention in several biotechnological applications owing to their ability to manipulate drug release characteristics in a controlled manner. Majority of these applications utilized N‐isopropylacrylamide (NIPAM)‐based particles for controlled drug release. Despite its advantages, such as easy chemical modification and well‐documented literature, a potentially important bottleneck for NIPAM in biological applications is its tendency for nonspecific protein adsorption. Herein, we report a simple way to prepare novel thermoresponsive colloids composed of oligo(ethylene glycol) side chains via precipitation polymerization technique. In addition to displaying highly reversible thermal response, these particles also have considerably low nonspecific protein adsorption when compared with NIPAM counterparts. These crosslinked poly(ethylene glycol) ethyl ether methacrylate particles were characterized using dynamic light scattering and transmission electron microscopy. The effects of co‐monomer, crosslinker and initiator on particle characteristics were investigated. Finally, particle toxicity studies were carried out using 3T3 fibroblast cell lines in MTT cytotoxicity assay. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Effect of Irrigation on the Oil Content and Fatty Acid Composition of Some Sunflower Seeds

The effect of irrigation on the seed yield, oil yield, and oil composition of sunflower in populations of Ekiz1 and VNIIMK 8931, a mixture of N₂, N₃, and N₄ lines, and a synthetic variety obtained from these lines has been studied. The major fatty acid was found to be oleic acid, in addition to linoleic, palmitic, and stearic acids. Irrigation increased seed yield, oil yield, and oil content of all samples. In two of them, the synthetic variety and VNIIMK 8931, the increase was found to be statistically significant. In addition, irrigation of the samples did not increase significantly the amount of oleic and linoleic acids. On the contrary, the amount of linoleic acid in the mixture of N₂, N₃, and N₄ lines and oleic acid in VNIIMK 8931 decreased statistically significantly.     

Poly(styrene‐b‐tetrahydrofuran)/clay nanocomposites by mechanistic transformation

Synthesis of poly(styrene‐block‐tetrahydrofuran) (PSt‐b‐PTHF) block copolymer on the surfaces of intercalated and exfoliated silicate (clay) layers by mechanistic transformation was described. First, the polystyrene/montmorillonite (PSt/MMT) nanocomposite was synthesized by in situ atom transfer radical polymerization (ATRP) from initiator moieties immobilized within the silicate galleries of the clay particles. Transmission electron microscopy (TEM) analysis showed the existence of both intercalated and exfoliated structures in the nanocomposite. Then, the PSt‐b‐PTHF/MMT nanocomposite was prepared by mechanistic transformation from ATRP to cationic ring opening polymerization (CROP). The TGA thermogram of the PSt‐b‐PTHF/MMT nanocomposite has two decomposition stages corresponding to PTHF and PSt segments. All nanocomposites exhibit enhanced thermal stabilities compared with the virgin polymer segments. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2190–2197, 2009