Phenotyping of CYP450 in human liver microsomes using the cocktail approach

The cocktail approach is an advantageous strategy used to monitor the activities of several cytochromes P450 (CYPs) in a single test to increase the throughput of in vitro phenotyping studies. In this study, a cocktail mixture was developed with eight CYP-specific probe substrates to simultaneously evaluate the activity of the most important CYPs, namely, CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and the CYP3A subfamily. After cocktail incubation in the presence of human liver microsomes (HLMs), the eight selected substrates and their specific metabolites were analyzed by ultra-high-pressure liquid chromatography and electrospray ionization quadrupole time-of-flight mass spectrometry. Qualitative and quantitative data were simultaneously acquired to produce an overview of the extended phase I biotransformation routes for each probe substrate in the HLMs and to generate phenotypic profiles of various HLMs. A comparison of the cocktail strategy with an individual substrate assay for each CYP produced similar results. Moreover, the cocktail was tested on HLMs with different allelic variants and/or in the presence of selective inhibitors. The results were in agreement with the genetic polymorphisms of the CYPs and the expected effect of the alterations. All of these experiments confirmed the reliability of this cocktail assay for phenotyping of the microsomal CYPs.     

Structure and properties of rhombohedral CePd3Ga8: A variant of the cubic parent compound with BaHg11 structure type

Single crystals of a new intermetallic gallide, R-CePd₃Ga₈, have been synthesized from excess molten gallium. Single-crystal X-ray diffraction reveals that R-CePd₃Ga₈ crystallizes in the R-3m space group with a=b=c=8.4903(10) Å and α=β=γ=89.993(17). R-CePd₃Ga₈ is a variant of the cubic BaHg₁₁ structure type with three structural units: a Ce-centered polyhedron, a distorted cube of Pd₂Ga₆ and a Pd-centered cuboctahedron. The distortions of these units are compared to undistorted analogous units in intermetallic compounds with BaHg₁₁ structure type. Field and temperature-dependent magnetization measurements on R-CePd₃Ga₈ reveal a paramagnetic material with strong antiferromagnetic correlations and a magnetization consistent with Ce³⁺. Electrical resistance measurements indicate Kondo behavior between localized Ce³⁺ magnetic moments.     

Multi-Product Expansion with Suzuki's Method:Generalization

In this paper we discuss the extension to exponential splitting methods with respect to time-dependent operators. We concentrate on the Suzuki's method, which incorporates ideas into the time-ordered exponential of [3, 11, 12, 34]. We formulate the methods with respect to higher order by using kernels for an extrapolation scheme. The advantages include more accurate and less computational intensive schemes for special time-dependent harmonic oscillator problems. The benefits of the higher order kernels are given on different numerical examples.     

Field-induced metal-insulator transition in a two-dimensional organic superconductor

The quasi-two-dimensional organic superconductor beta"-(BEDT-TTF)2SF5CH2CF2SO3 (Tc approximately 4.4 K) shows very strong Shubnikov-de Haas (SdH) oscillations which are superimposed on a highly anomalous steady background magnetoresistance, Rb. Comparison with de Haas-van Alphen oscillations allows a reliable estimate of Rb which is crucial for the correct extraction of the SdH signal. At low temperatures and high magnetic fields insulating behavior evolves. The magnetoresistance data violate Kohler's rule, i.e., cannot be described within the framework of semiclassical transport theory, but converge onto a universal curve appropriate for dynamical scaling at a metal-insulator transition.     

External short-cavity diode-laser for MIR difference-frequency generation

A compact mid-infrared (MIR) laser system is described applying two single mode diode-lasers as pump and signal sources to generate difference-frequency radiation in AgGaS₂. A spectral tuning range of 71.5 cm^-1 between 4.9–5.1 m with an output power of 100 nW and linewidth of 1.2×10^-2 cm^-1 (3.6 GHz) for the DFG laser system is obtained by mode behavior improvement of the pump source using an external short-cavity. The performance of such an external short-cavity MIR-DFG laser spectrometer is demonstrated by recording the fundamental absorption spectra of carbon monoxide (¹²C¹⁶O) and nitric oxide (¹⁴N¹⁶O) in a 10 cm long cell in order to estimate line-broadening coefficients of CO and NO molecules, which are of general interest in combustion diagnostics . PACS 32.20.-t; 33.20.Ea; 42.60-v; 42.60.Fc; 42.62.-b; 42.62.Fi; 42.68.-w; 42.68.Ca; 42.72.-g; 42.72.Ai     

Validation of capillary electrophoresis--mass spectrometry methods for the analysis of a pharmaceutical formulation

The coupling of capillary electrophoresis (CE) to mass spectrometry (MS) with an electrospray ionization (ESI) technique is generally performed for qualitative applications, and only few quantitative results have been reported. This paper investigates the validation of a CE-ESI-MS method for the analysis of a pharmaceutical formulation containing lidocaine. Some important ESI criteria are discussed including sheath-liquid composition, nebulizing gas pressure and position of the CE capillary outlet. After optimization of these parameters, an intermediate precision of about 5% was achieved. The latter, as well as efficiency and resolution, were compared to those achieved with UV detection. Besides, a multiple injection procedure was developed to reduce analysis time per sample and was successfully applied to both UV and MS detectors. The validation results achieved by multiple injections were identical to those obtained with classical injection, but afforded a gain of time by a factor of 2.5.