Pharmaceutical Applications on Columns Packed with Sub-2 µm Particles

During the last few years, there has been a great interest in the development of fast liquid chromatography. Among the reported approaches, the reduction of the particle size to attain sub-2µm diameter represents a good solution for achieving both increased separation power and faster analysis time. This paper demonstrates the chromatographic performance of such supports using plateheight curves and reveals the possibility for obtaining ultra-fast or highly efficient separations, according to the column geometry and system pressure limitations. The stability of these columns is initially evaluated using a system suitability experiment. The chromatographic performance remains stable in terms of retention, efficiency, and pressure for more than 1700 injections with pressure conditions ranging from 200 to 800 bar. Several fast and ultra-fast pharmaceutical applications are reported. In isocratic mode, a 5- to 10-fold reduction in analysis time is obtained with limited influence on efficiency and resolution. The run time is further reduced by 30-fold with the shorter available columns (i.e., 30 mm length). In gradient mode, the separation of a complex mixture containing an active pharmaceutical compound and related impurities is significantly improved with column length equal to 100 mm, to increase peak capacity and resolutio

BioCreative III interactive task: an overview

The BioCreative challenge evaluation is a community-wide effort for evaluating text mining and information extraction systems applied to the biological domain. The biocurator community, as an active user of biomedical literature, provides a diverse and engaged end user group for text mining tools. Earlier BioCreative challenges involved many text mining teams in developing basic capabilities relevant to biological curation, but they did not address the issues of system usage, insertion into the workflow and adoption by curators. Thus in BioCreative III (BC-III), the InterActive Task (IAT) was introduced to address the utility and usability of text mining tools for real-life biocuration tasks. To support the aims of the IAT in BC-III, involvement of both developers and end users was solicited, and the development of a user interface to address the tasks interactively was requested

Method transfer for fast liquid chromatography in pharmaceutical analysis: application to short columns packed with small particle. Part I: isocratic separation

Liquid chromatography (LC) is considered to be the gold standard in pharmaceutical analysis. Today, there is a need for fast and ultra-fast methods with good efficiency and resolution for achieving separations in few minutes or even seconds. The present work describes a simple methodology for performing a successful method transfer from conventional LC to fast and ultra-fast LC. In order to carry out fast separations, short columns (20-50mm) packed with small particles (3.5 and 1.7 microm) were used and their chromatographic performance was compared to that of a conventional column (150 mm, 5 microm). For that purpose, an optimized LC system was employed to limit extra-column volumes which can have a dramatic impact on efficiency and resolution. This paper reports the fundamental equations used for transferring an isocratic chromatographic separation performed with a given column geometry and chemistry to a smaller column packed with similar or identical stationary phase, without influence on chromatographic performance. For this purpose, the flow rate and the injected volume need to be adapted. The effect of column length and particle size reduction on chromatographic resolution and analysis time was described for an isocratic separation. Using the method transfer equations, it is possible to predict the new conditions to be used, for fast and ultra-fast separations. In this work, ultra-fast separations were achieved thanks to a new generation of instrumentation (ultra performance liquid chromatography, UPLC) which uses simultaneously short column packed with sub-2 microm particles and ultra-high pressure (up to 1000 bar). This work demonstrates an analysis time reduction up to a factor 12, compared to a conventional LC separation, without affecting the quality of separation. Therefore, the complete resolution of a pharmaceutical formulation was achieved in only a few seconds

New trends in fast liquid chromatography

Analytical laboratories are currently interested in enhancing overall productivity by increasing sample throughput and reducing analysis time. Different approaches are proposed in liquid chromatography (LC) to perform fast or ultra-fast separations with cycle times of less than 5 or 1 min, respectively. Among these approaches, the use of monolithic supports, high temperature LC (HTLC), short columns and ultra-performance LC (UPLC) are described and compared in this study. A comparison of the above LC approaches is presented through Knox curves and pressure plots based on experimental data. Fast separations of pharmaceutical compounds are presented in order to illustrate the interest of these techniques and compare them with conventional LC separations

Recent developments in liquid chromatography--impact on qualitative and quantitative performance

In order to reduce the analysis time and maintain good efficiency in liquid chromatography (LC), several solutions are currently being investigated. The focus of this study was to compare, both qualitatively and quantitatively, the chromatographic performance of a conventional LC with selected approaches, namely monolithic supports, high temperature LC (up to 90 degrees C), and sub-2 microm particles combined with high pressure (up to 1000 bar). This comparison was achieved from a qualitative point of view with a special attention paid to the analysis of time reduction, efficiency improvement, and pressure constraint. For this purpose, the different approaches were discussed using Knox curves and other kinetic plots. It appeared that columns packed with sub-2 microm particles under high-pressure conditions (UPLC) were well adapted and this option represents an attractive alternative to conventional LC; however, the other alternative approaches should not be neglected. The quantitative evaluation of these techniques was performed on the basis of the validation of results of a pharmaceutical formulation (Rapidocaïne), following SFSTP 2003 guidelines. Fast-LC approaches demonstrated equivalent performance to conventional LC in terms of trueness, precision, and accuracy profile, with a significant time reduction (up to 8x) according to the selected methodology

Single-trial cross-area neural population dynamics during long-term skill learning

Learning skilled movements requires evolution in neural population dynamics both within and across cortical regions. Here, the authors combine simultaneous recordings of motor and premotor cortex with computational methods to show that single-trial cross-area dynamics correlate with single-trial behavior performance and skill acquisition

Chromatographic behaviour and comparison of column packed with sub-2 microm stationary phases in liquid chromatography

In order to reduce the analysis time and maintain good efficiency in liquid chromatography, it is advisable to simultaneously decrease the column length and the particle size of the chromatographic support. Therefore, several manufacturers have developed and commercialized short columns filled with particles that have a diameter smaller than 2 microm. The focus of this work was to check the chromatographic performance of such columns and compare possibilities offered by sub-2 microm supports with conventional columns in terms of analysis time reduction and efficiency improvements. For this purpose, different parameters were discussed namely: separation impedance (E), Knox curves (h,v), and number of plates by time unit (N/t0). Kinetic plots were also drawn. It appeared that sub-2 microm supports were well adapted to improve chromatographic performance and to reduce the analysis time. Furthermore, it was also demonstrated that the best chromatographic performances were reached with high pressure systems (up to 1000 bar)

Fast analysis in liquid chromatography using small particle size and high pressure

In order to enhance chromatographic performances in terms of efficiency and rapidity, LC has recently evolved in the development of short columns packed with small particles (sub-2 microm) working at high pressures (> 400 bar). This approach has been described 30 years ago according to the fundamental chromatographic equations. However, systems and columns compatible with such high pressures have been introduced in the market in 2004 only. Advantages of small particles working at high pressure will be discussed in terms of sensitivity, efficiency, resolution, and analysis time. Potential problems encountered with high pressure in terms of frictional heating and solvent compressibility will also be discussed even if systems working at a maximum pressure of 1000 bar are not influenced by these parameters and give reliable and reproducible results. Several applications will highlight the potential and interest of this new technology