Screening approach for chiral separation of pharmaceuticals IV. Polar organic solvent chromatography

The aim of this work is to determine generic screening conditions and an initial simple separation strategy allowing the rapid separation of drug enantiomers in polar organic solvent chromatography (POSC). Four cellulose/amylose-based stationary phases were investigated in detail using two mobile phase basis solvents commonly applied in this mode, i.e. acetonitrile and methanol. Polar mode is interesting for use in purification of enantiomers. In a first step, the parameters potentially influencing the separation, such as addition of an alcohol to the polar organic solvent or the type of mobile phase additive(s), were examined by means of experimental designs. Afterwards, the factors found most important are investigated in more detail. Results showed that the cellulose- and amylose-based stationary phases have very broad and complementary enantiorecognition abilities in the POSC mode. The type of organic solvent for the mobile phase appeared to have a dramatic influence on the quality of the separation. Based on the results, a screening strategy was proposed. Enantioseparation was observed in more than 85% of the tested compounds and analysis times of last eluted peak were usually below 10 min.     

Precision study on capillary electrophoresis methods for metacycline

A CE method for metacycline (MTC) determination was investigated in an inter-laboratory experiment. Many problems were encountered in this study, most of which were related to the transfer of the method to different CE equipment. The reported problems could be classified into different categories: problems related to the precision, to the parameters in the protocol, and to the MTC peak shape. As the peak shape problem was partially responsible for the poor precision, a new CE method was developed in order to obtain a good MTC peak shape on all equipment. The precision of this new method for MTC determination was examined in an intermediate precision study, where the influence of the factors "time" and "equipment" was investigated. Although the new method could be transferred to different instruments, the precision remained poor mainly due to the contributions of the between-replicate and the between-injection variances.     

Hydrogels Incorporating GdDOTA: Towards Highly Efficient Dual T(1) /T(2) MRI Contrast Agents

Do not tumble dry: Gadolinium-DOTA encapsulated into polysaccharide nanoparticles (GdDOTA?NPs) exhibited high relaxivity (r(1) =101.7?s(-1) mM(-1) per Gd(3+) ion at 37?°C and 20?MHz). This high relaxation rate is due to efficient Gd loading, reduced tumbling of the Gd complex, and the hydrogel nature of the nanoparticles. The efficacy of the nanoparticles as a T(1) /T(2) dual-mode contrast agent was studied in C6 cells.     

Self and N2 collisional broadening of far-infrared methane lines measured at the SOLEIL synchrotron

Following our recent study devoted to measurements of intensities of pure rotation lines of methane, room temperature far infrared spectra of methane diluted in nitrogen at five total pressures between 100 and 800 hPa have been recorded at the AILES beamline of the SOLEIL synchrotron. One hundred and five N₂ broadening coefficients of methane pure rotation lines have been measured in the 83–261 cm^?1 spectral range using multi-spectrum non-linear least squares fitting of Voigt profiles. Pressure-induced line shifts were not needed to fit the spectra to the noise level and line mixing effects were neglected. One hundred and seventy-six self broadening coefficients have also been measured in the 59–288 cm^?1 spectral range using the pure methane spectra recorded in our previous work. The measured N₂ broadening coefficients were compared to semi-classical calculations.     

Synthesis of benzyl substituted naphthalenes from benzylidene tetralones

A convenient and efficient synthesis of novel highly substituted dimethoxybenzylnaphthalenes, which are precursors to several dihydroxynaphthoic acids, is described. The approach involves the use of aldol chemistry to provide a number of benzylidene tetralones, which are converted to the target naphthalenes in three steps, with good to excellent yields. Grignard reaction of intermediate benzyl tetralones provided 1-substituted benzyl naphthalenes. The reported synthesis is flexible and scalable and provides access to naphthalenes having a variety of substitution patterns. These benzyl substituted naphthalenes are being converted to naphthoic acids and the bioactivities of these compounds are currently being investigated.     

Transformations of Gibbs measures

We study local transformations of Gibbs measures. We establish sufficient conditions for the quasilocality of the images and obtain results on the existence and continuity properties of their relative energies. General results are illustrated by simple examples. Received: 11 November 1997 / Revised version: 20 February 1998     

Protective inventories and bottlenecks in production systems

In this paper we study the allocation of safety stocks and safety times in multi-echelon production systems. We concentrate on the impact of demand uncertainty on the amount of safety stocks in the presence of capacity constraints. We describe how this problem can be viewed as a Markovian Decision Process. The form of the optimal policies is discussed and illustrated with examples.     

Preface

Numerical Algorithms -     

Roll cutting in the curtain industry,or: A well-solvable allocation problem

We study the problem of cutting a number of pieces of the same length from n rolls of different lengths so that the remaining part of each utilized roll is either sufficiently short or sufficiently long. A piece is ‘sufficiently short’, if it is shorter than a pre-specified threshold value δ_min, so that it can be thrown away as it cannot be used again for cutting future orders. And a piece is ‘sufficiently long’, if it is longer than a pre-specified threshold value δ_max (with δ_max > δ_min), so that it can reasonably be expected to be usable for cutting future orders of almost any length. We show that this problem, faced by a curtaining wholesaler, is solvable in O(nlogn) time by analyzing a non-trivial class of allocation problems.