A simple high pH liquid chromatography-tandem mass spectrometry method for basic compounds: application to ephedrines in doping control analysis

Solvent systems for use with LC-MS often result in a compromise between chromatographic performance and mass spectrometric detection, exemplified here by a LC-MS/MS method development for the analysis of ephedrines in doping control. Ephedrines, frequently found in therapeutic and nutritional preparations, are among the most commonly administered doping agents in competitive sport. Improved separation of these hydrophilic, basic compounds, some of which are diastereoisomers, is achieved in reversed-phase LC by the use of a high pH mobile phase in order to suppress analyte ionisation, and thus alter their polarity, resulting in reduced peak tailing and enhanced retention. However, when coupled to an ESI-MS detector, this eluent composition generated a non-linear and poorly reproducible signal. APCI yielded greater stability and reproducibility and is here presented as an ion source for the analysis of basic compounds under conditions that suppress their ionisation. Errors as large as 49.3% were observed with ESI, compared with 15.4% generated using APCI, for pseudoephedrine over the calibration range (25-400 μg/mL) in urine with a simple dilution and injection of samples. These data highlight the importance of suitable MS conditions for stable performance, necessary for accurate quantification, without undue compromise to the LC separation.     

Gradient elution in counter-current chromatography: a new layout for an old path

Gradient elution in CCC is a powerful tool, which needs further systematic development to become robust and easy to use. The first attempt to build a correlation between gradient elution profile and distribution ratio (K(D)) values for model mixtures containing typical representatives of pharmaceutical compounds is presented in this paper. The three step estimation of the solvent system composition of a heptane-ethyl acetate-methanol-water (HEMWat) series is described. The estimation is based on simple measurements of initial and final stationary phase retention for gradient elution run, calculating gradient distribution ratio and correlating it with static K(D) against HEMWat number.     

Kinetic Resolution of (R,S)-2-Butanol Using Enzymatic Synthesis of Esters

Kinetic resolution of (R,S)-2-butanol using enzymatic synthesis of esters has been studied. (R,S)-2-Butanol is commonly found as a racemic mixture, and the products of its esterification are racemic mixtures too. This work is of great significance in the field of the enzymatic kinetic resolution due to the little information found in literature about the resolution of (R,S)-2-butanol as pure compound. So, this article is a contribution about the enzymatic resolution of (R,S)-2-butanol. The reaction here studied is the esterification/transesterification of (R,S)-2-butanol in organic media (n-hexane) using as biocatalyst the lipase Novozym 435?. The main target of this study is to analyze the influence of certain variables in this reaction. Some of these variables are acyl donor (acids and esters), concentration of substrates, enzyme/substrate ratio, and temperature. The main conclusions of this study are the positive effect of higher substrates concentration (1.5 M) and larger amount of enzyme (13.8 g mol(-1) substrate) on kinetic resolution rate but not a very noticeable effect on enantiomeric excesses. The longer the carboxylic acid chain is, the better results are obtained. Besides to achieve a satisfactory kinetic resolution, it is recommendable to select reaction times (180 min) at which the highest substrate enantiomeric excess is reached (~60%). The temperature has not an appreciable influence on the resolution in the range studied (40-60 °C). When an ester (vinyl acetate) is used as acyl donor, the resolution shows better results than when using a carboxylic acid as acyl donor (ee(s)?~90% at 90 min). Moreover, Michaelis-Menten parameters, v(max) and K(M), were determined, 0.04 mol l(-1) min(-1) and 0.41 mol l(-1), respectively.     

Chemistry at boron: synthesis and properties of red to near-IR fluorescent dyes based on boron-substituted diisoindolomethene frameworks

A general method for the synthesis of difluorobora-diisoindolomethene dyes with phenyl, p-anisole, or ethyl-thiophene substituents has been developed. The nature of the substituents allows modulation of the fluorescence from 650 to 780 nm. Replacement of the fluoro ligands by ethynyl-aryl or ethyl residues is facile using Grignard reagents. Several X-ray molecular structures have been determined, allowing establishment of structure-fluorescence relationships. When the steric crowding around the boron center is severe, the aromatic substituents α to the diisoindolomethene nitrogens are twisted out of coplanarity, and hypsochromic shifts are observed in the absorption and emission spectra. This shift reached 91 nm with ethyl substituents compared to fluoro groups. When ethynyl linkers are used, the core remains flat, and a bathochromic shift is observed. All the fluorophores exhibit relatively high quantum yields for emitters in the 650-800 nm region. When perylene or pyrene residues are connected to the dyes, almost quantitative energy transfer from them to the dye core occurs, providing large virtual Stokes shifts spanning from 8000 to 13,000 cm(-1) depending on the nature of the dye. All the dyes are redox active, providing the Bodipy radical cation and anion in a reversible manner. Stepwise reduction or oxidation to the dication and dianion is feasible at higher potentials. We contend that the present work paves the way for the development of a new generation of stable, functionalized luminophores for bioanalytical applications.     

On the Initial Conditions and Solutions of the Semiclassical Einstein Equations in a Cosmological Scenario

In this paper we shall discuss the backreaction of a massive quantum scalar field on the curvature, the latter treated as a classical field. Furthermore, we shall deal with this problem in the realm of cosmological spacetimes by analyzing the Einstein equations in a semiclassical fashion. More precisely, we shall show that, at least on small intervals of time, solutions for this interacting system exist. This result will be achieved providing an iteration scheme and showing that the series, obtained starting from the massless solution, converges in the appropriate Banach space. The quantum states with good ultraviolet behavior (Hadamard property), used in order to obtain the backreaction, will be completely determined by their form on the initial surface if chosen to be lightlike. Furthermore, on small intervals of time, they do not influence the behavior of the exact solution. On large intervals of time the situation is more complicated but, if the spacetime is expanding, we shall show that the end-point of the evolution does not depend strongly on the quantum state, because, in this limit, the expectation values of the matter fields responsible for the backreaction do not depend on the particular homogeneous Hadamard state at all. Finally, we shall comment on the interpretation of the semiclassical Einstein equations for this kind of problems. Although the fluctuations of the expectation values of pointlike fields diverge, if the spacetime and the quantum state have a large spatial symmetry and if we consider the smeared fields on regions of large spatial volume, they tend to vanish. Assuming this point of view the semiclassical Einstein equations become more reliable.     

Sharp continuity results for the short-time Fourier transform and for localization operators

We completely characterize the boundedness on Wiener amalgam spaces of the short-time Fourier transform (STFT), and on both L ^p and Wiener amalgam spaces of a special class of pseudodifferential operators, called localization operators. Precisely, sufficient conditions for the STFT to be bounded on the Wiener amalgam spaces W(L ^p , L ^q ) are given and their sharpness is shown. Localization operators are treated similarly: using different techniques from those employed in the literature, we relax the known sufficient boundedness conditions for these operators to be bounded on L ^p spaces and prove the optimality of our results. Next, we exhibit sufficient and necessary conditions for such operators to be bounded on Wiener amalgam spaces.     

Hardy–Sobolev Type Inequalities with Sharp Constants in Carnot–Carathéodory Spaces

We prove a generalization with sharp constants of a classical inequality due to Hardy to Carnot groups of arbitrary step, or more general Carnot–Carathéodory spaces associated with a system of vector fields of Hörmander type. Under a suitable additional assumption (see Eq. 1.6 below) we are able to extend such result to the nonlinear case \(p\not= 2\). We also obtain a sharp inequality of Hardy–Sobolev type.     

Magnetic resonance diffusion-weighted imaging: quantitative evaluation of age-related changes in healthy liver parenchyma

The purpose of this study was to verify in healthy liver parenchyma the possible influence of age on DwI-related parameters: apparent diffusion coefficient (ADC), perfusion fraction (PF), diffusion and pseudodiffusion coefficient (D and D^?). Forty healthy adult volunteers (age range 26-86 years), divided into four age groups, were prospectively submitted to a breath-hold magnetic resonance diffusion imaging (MR-DwI) (two b values, 0-300 and 0-1000 s/mm²). A smaller cohort of 16 subjects underwent a free-breath multi-b acquisition (16 b values, 0-750 s/mm²). Quantitative analysis was performed by two observers with manually defined regions of interest, on the most homogeneous portion of the right liver lobe. Individual and group statistical analysis of data was performed: ANOVA to establish differences between groups and Pearson correlation coefficient to investigate the association between DwI parameters and age. The mean, S.D. and 95% limits of agreement of ADC values for each age-defined group are reported. ANOVA showed no significant differences between group means (P always >.05). No significant correlation between subjects' age and DwI parameters was established, both in breath-hold and free-breath acquisitions, on the whole range of adopted b values. Our study conducted on healthy liver parenchyma shows that there are no significant differences in ADC, PF, D and D^? of younger or older subjects.     

Influence of the counterion on the synthesis of ZnO mesocrystals under solvothermal conditions

Polymers and coordinating solvents have been shown to serve as templating agents to assist the precipitation of ZnO nanoparticles and address their morphology. In this work we show for the first time that a difference in the coordination strength between the polymer (poly‐N‐vinylpyrrolidone (PVP)) and the two Zn^II precursor salts (nitrate and acetate) is able to promote or suppress the formation of mesocrystalline structures and even more importantly to tune their three‐dimensional organization. On the basis of FTIR and ¹³C NMR spectroscopic studies, we propose that not only the polymer (PVP) but also the solvent (DMF) play a key role as directing agents.