Identification of In Vitro Metabolites of Amoxicillin in Human Liver Microsomes by LC–ESI/MS

Amoxicillin (AMOX) metabolism in human liver microsomes was studied in vitro using liquid chromatography–mass spectrometry (LC/MS). Amoxicillin was incubated with human liver microsomes along with NADPH, and the reaction mixture was analyzed by LC/MS to obtain the specific metabolic profile of the studied antibiotic drug. Positive electrospray ionization was employed as the ionization source. An ACE C18-column (4.6 mm × 150 mm, 3 μm) was implemented with acetonitrile and water (+0.1 % formic acid) in isocratic mode as the mobile phase at the flow 0.4 mL min^?1. The chemical structures of metabolites were proposed on the basis of the accurate mass measurement of the protonated molecule as well as their main product. Six phase I and one phase II metabolites were detected and structurally described. The metabolism of AMOX occurred via oxidation, hydroxylation and oxidative deamination, as well as through combination of these reactions. Compound M7, with glucuronic acid was also observed as phase II metabolite. Neither sulfate nor glutathione conjugates were detected. This study presents novel information about the chemical structure of the potential AMOX metabolites and provides vital data for further pharmacokinetic and in vivo metabolism studies.     

Thermal properties of silica/poly(2,6-dimethyl-1,4-phenylene oxide) films prepared by emulsion polymerization

Thermal properties of the silica/poly(2,6-dimethyl-1,4-phenylene oxide) films prepared via emulsion polymerized mixed matrix (EPMM) method are investigated, and the impact of the synthesis protocol on the silica content, compatibility between the organic and inorganic phases, and the thermal stability of these nanocomposites is studied. Two series of films, namely EPMM-1S and EPMM-2S, synthesized in one- and two-step process, respectively, with different combinations of surfactant and compatibilizer were prepared. The polymerization of the silica precursor in the films was confirmed by ²⁹Si nuclear magnetic resonance, and its content was investigated by inductively coupled plasma mass spectroscopy analysis. Thermal properties of the EPMM films were investigated by differential scanning calorimetry and thermogravimetric analysis. The glass transition temperature (T _g) of EPMM films was greater compared to the neat PPO film. However, an increase in T _g was not related to the concentration of silica in the film, but rather to the quality of dispersion of synthesized nanoparticles. Despite a lower inorganic loading, EPMM-1S films had a greater T _g than EPMM-2S films. On the other hand, both the decomposition temperature and the activation energy for the decomposition were directly related to the silica content in the EPMM films. In general, regardless of the synthesis protocol, the presence of compatibilizer (ethanol) leads to greater inorganic content and improved thermal properties of the EPMM films.     

Strong decay to equilibrium in one-dimensional random spin systems

We consider a spin system on a lattice with finite-range, possibly unbounded random interactions. We show that for such systems the Glauber dynamics cannot decay to equilibrium exponentially fast inL ₂ even at high temperatures. Additionally, for one-dimensional systems with unbounded random couplings we prove that with probability one the corresponding Glauber dynamics has a fast (subexponential) decay to equilibrium in the uniform norm, provided that the distribution of random couplings satisfies some exponential bound.     

Palladium(0)-Mediated Synthesis of Acetylated Unsaturated 1,4-Disaccharides

Abstract

Alkylation of ethyl 6-O-tert-butyldiphenylsilyl-4-O-methoxycarbonyl-2,3-dideoxy-α-D-erythro-hex-2-enopyranoside (1) with various peracetylated 1-hydroxy sugars in the presence of a catalytic amount of palladium(O) gave the corresponding unsaturated 1,4-disaccharides and trisaccharides. In all cases the reaction is regio- and stereospecific according to the unsaturated moiety, alkylation occuring only at C-4 of the unsaturated carbohydrate, with overall retention of configuration.     

Pharmacokinetic study of amoxicillin in human plasma by solid‐phase microextraction followed by high‐performance liquid chromatography–triple quadrupole mass spectrometry

Sensitive and selective analytical procedures based on high‐performance liquid chromatography with mass spectrometric detection were developed for the determination of amoxicillin in human plasma samples. Samples were prepared by applying in‐house manufactured molecularly imprinted solid‐phase microextraction probes. The detection of target compounds was performed in multiple reaction monitoring mode. The multiple reaction monitoring detection was operated in the positive electrospray ionization mode using the transitions of m/z 366 ([M + H]⁺) → 349 for amoxicillin and m/z 390 ([M + H]⁺) → 372 for gemifloxacin. The method was validated with precision within 15% relative standard deviation and accuracy within 15% relative error. The method was successfully applied to study of the pharmacokinetics of amoxicillin in human plasma after oral administration of amoxicillin. Copyright © 2013 John Wiley & Sons, Ltd.     

Influence of temperature on mass transfer in an incomplete trapping supported liquid membrane extraction of triazole fungicides

The influence of temperature in a supported liquid membrane (SLM) extraction of triazole fungicides was investigated. The mass transfer parameters such as diffusion coefficient, flux and apparent viscosity were determined at temperatures ranging from 5 to 40°C. Increase in temperature led to an increase in diffusion coefficient and flux with a flowing acceptor solution. The apparent viscosity also decreased with an increase in temperature. However, the increase in mass transfer parameters did not result in an overall increase in extraction efficiency with a stagnant or circulation acceptor phase. Stripping of the analytes from the membrane into the acceptor phase as well as the configuration of the extraction unit could have limited the influence of temperature on mass transfer. The partition coefficient of analytes from the acceptor solution to the membrane, K_A, was found to be much higher than that from the donor solution to the membrane K_D, thus triazole compounds preferred to remain in the membrane even with an increased extraction temperature.     

The effect of stationary phase on lipophilicity determination of beta-blockers using reverse-phase chromatographic systems

Evaluation of lipophilicity parameters for basic compounds using different chromatographic stationary phases is presented. An HPLC method for determination of lipophilic molecule-stationary phase interactions was based on gradient analysis. Differences in correlation between the lipophilicity of compounds and experimental chromatographic results obtained in pseudo-membrane systems showed a strong influence of stationary phase structure and physico-chemical properties. beta-Blocker drugs with varying lipophilicity and bio-activity were chosen as test compounds. The stationary phases used for the study were monolithic rod-structure C18 and silica gel octadecyl phase SG-C18 as reference material. The second group was silica gel-based polar-embedded alkylamide and cholesterolic phases. The mobile phase was composed of acetonitrile or methanol with ammonium acetate, and a linear gradient of methanol and acetonitrile in mobile phase was performed. A linear correlation of plots of log k(g) = f(log P) was observed, especially for polar-embedded phases, and this allowed log P(HPLC) to be calculated. The behavior of stationary phases in methanol and acetonitrile buffer showed differences between obtained log P(HPLC) values.     

On log-Sobolev inequalities for infinite lattice systems

For a system on an infinite lattice, we show that a Gibbs measure for a smooth local specification ={E } satisfying the Dobrushin uniqueness theorem also satisfies log-Sobolev inequality, provided it is satisfied for one-dimensional measures E _l .