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71.
In vitro ketamine CYP3A‐mediated metabolism study using mammalian liver S9 fractions,cDNA expressed enzymes and liquid chromatography tandem mass spectrometry 下载免费PDF全文
Raphaël Santamaria Floriane Pailleux Francis Beaudry 《Biomedical chromatography : BMC》2014,28(12):1660-1669
Ketamine is widely used in medicine in combination with several benzodiazepines, including midazolam. The objectives of this study were to develop a novel HPLC‐MS/selected reaction monitoring (SRM) method capable of quantifying ketamine and norketamine using an isotopic dilution strategy in biological matrices and study the formation of norketamine, the principal metabolite of ketamine with and without the presence of midazolam, a well‐known CYP3A substrate. The chromatographic separation was achieved using a Thermo Betasil Phenyl 100 × 2 mm column combined with an isocratic mobile phase composed of acetonitrile, methanol, water and formic acid (60:20:20:0.4) at a flow rate of 300 μL/min. The mass spectrometer was operating in selected reaction monitoring mode and the analytical range was set at 0.05–50 μm . The precision (CV) and accuracy (NOM) observed were 3.9–7.8 and 95.9–111.1% respectively. The initial rate of formation of norketamine was determined using various ketamine concentrations and Km values of 18.4, 13.8 and 30.8 μm for rat, dog and human liver S9 fractions were observed, respectively. The metabolic stability of ketamine on liver S9 fractions was significantly higher in human (T1/2 = 159.4 min) compared with rat (T1/2 = 12.6 min) and dog (T1/2 = 7.3 min) liver S9 fractions. Moreover significantly lower IC50 and Ki values observed in human compared with rat and dog liver S9 fractions. Experiments with cDNA expressed CYP3A enzymes showed that the formation of norketamine is mediated by CYP3A but results suggest an important contribution from other isoenzymes, most likely CYP2C particularly in rat. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
72.
Tonka Vasileva Ilia Iliev Myriam Amari Veselin Bivolarski Marie-Sophie Bounaix Hervé Robert Sandrine Morel Philippe Rabier Iskra Ivanova Bruno Gabriel Catherine Fontagné-Faucher Valérie Gabriel 《Applied biochemistry and biotechnology》2012,168(3):718-730
Glycosyltransferase activity of 13 Leuconostoc mesenteroides strains isolated from Bulgarian fermented vegetables was investigated. All the strains displayed a mucoid phenotype on sucrose-containing agar media. Strains were characterized according to carbohydrate fermentation, species-specific multiple PCR using several primers, repetitive element-PCR fingerprinting using (GTG)5 primers and glycosyltransferase activity. Level of activity and cellular localization (soluble or cell-associated) were variable among strains. Precipitation of exopolysaccharides produced from sucrose by the soluble fractions from these strains allowed recovery of only glucans and further characterization by 1H and 13C NMR analysis and enzymatic digestion with dextranase revealed dextran production. However, levans could be detected in presence of raffinose as fructosyl donor. Both fructosyltransferase and glucosyltransferase encoding genes were detected by PCR and both active enzymes were detected after functional characterization by SDS-PAGE electrophoresis and in situ polymer production after incubation with sucrose. This work therefore showed that concomitant production of glucosyltransferase and fructosyltransferase is widespread in L. mesenteroides strains. 相似文献
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Jeong SC Herrmann N Fan ZG Freifelder R Gobbi A Hildenbrand KD Krämer M Randrup J Reisdorf W Schüll D Sodan U Teh K Wessels JP Pelte D Trzaska M Wienold T Alard JP Amouroux V Basrak Z Bastid N Belayev IM Berger L Bini M Blaich T Boussange S Buta A Caplar R Cerruti C Cindro N Coffin JP Dona R Dupieux P Erö J Fintz P Fodor Z Fraysse L Frolov S Grigorian Y Guillaume G Hölbling S Houari A Jundt F Kecskemeti J Koncz P Korchagin Y Kotte R Kuhn C Ibnouzahir M Legrand I Lebedev A Maguire C Manko V 《Physical review letters》1994,72(22):3468-3471
76.
The synthesis of 10H-pyrrolo[1,2-a]thieno[3,4-e][1,4]diazepin-5(4H)-one ( 16 ) and some derivatives are described from methyl 3-bromomethylthiophene-4-carboxylate ( 5 ). The key step of these sequences is the intramolecular cyclization of the carbonylazides 12 and 13 . 相似文献
77.
We calculate, to first order in QCD, the probability for a fast hadron observed at laboratory angle θ h from the virtual photon directionq, to originate from the quark of a quark-gluon final state. Given this probability, the average gluon energy and angle with respect toq are then calculated. This approach provides a method for gluon jet direction in forthcoming experiments. 相似文献
78.
The volumes, heat capacities, and enthalpies of solution of adamantane in cycloxane,n-hexane, and carbon tetrachloride have been measured as a function of concentration at 25°C (15, 25, and 35°C for the volumes). The results extrapolated to infinite dilution have been resolved into cavity formation and interaction terms. The former have been calculated from the equations of the scaled-particle theory. To estimate the contribution from the latter, we have assumed some proportionality between adamantane-solvent and cyclohexane-solvent interactions. This assumption has been verified with the three different solvents for the three studied thermodynamic functions. The diameter of adamantane in solution has been determined to be 6.36 Å. 相似文献
79.
Reactions of substituted cyanoacetate anions 4 with S,S-dialayklsuccinimidosulfonium salts resulted generally in the formation of N-alkylthiomethylketenimines and α-alkylthiomethylesters. Coupling products were also obtained with anion 4d and only observed in the case of methyl phenylcyanoacetate anion 4b. The results were interpreted by the formation of instable σ-sulfurane intermediates. Homolytic cleavage of these intermediates gave radical pairs, then the coupling products. Heterocyclic clevage gave new sulfonium salts which rearranged via sulfonium ylides. 相似文献
80.
Reactions of 5-phenylthieno[3,2-b]pyran-7-one, 2-phenylbenzo[b]-thieno[3,2-b]pyran-4-one and the corresponding thiones with sodium ethylate, guanidines, hydrazines and amines are described and compared to those observed with benzopyranones. 相似文献