1,721,264 research outputs found
DETERMINATION OF IN VITRO AND IN SILICO INDEXES FOR THE MODELLING OF BLOOD-BRAIN BARRIER PARTITIONING OF DRUGS VIA MICELLAR AND IMMOBILIZED ARTIFICIAL MEMBRANE LIQUID CHROMATOGRAPHY
Get PDFIn the present work, 79 structurally unrelated analytes were taken into account and their chromatographic retention coefficients, measured by Immobilized Artificial Membrane Liquid Chromatography (IAM-LC), and by Micellar Liquid Chromatography (MLC) employing sodium dodecyl sulfate (SDS) as surfactant, were determined. Such indexes were subsequently used for the development of Blood-Brain Barrier passage-predictive statistical models using partial least square (PLS) regression along with topological and physico-chemical parameters, calculated in silico. Highly significant relationships were observed either using IAM (r2 (n-1) = 0.78) or MLC (r2 (n-1) = 0.83) derived indexes along with in silico descriptors. This hybrid approach proved fast and effective in the development of highly predictive BBB passage oriented models and, therefore, it can be of interest for pharmaceutical industries as a high-throughput BBB penetration oriented screening method. Finally, it offered interesting insights into the molecular mechanism actually involved in the BBB permeation of drugs
Entry of therapeutics into the brain: Influence of exposed polarity calculated in silico and measured in vitro by supercritical fluid chromatography
No full textThe present work proposes a novel application of EPSA (not an acronym but found to be referred to by many as
Exposed Polar Surface Area), a supercritical fluid chromatography (SFC) polarity readout for assisting in the
prediction of the extent of drug permeation through the blood-brain barrier (BBB). For this purpose, EPSA values
for 69 structurally unrelated acidic, basic, neutral and amphoteric compounds were determined by a validated
SFC method. Additionally, water-accessible surface area (WASA) values for the whole dataset were calculated in
silico and compared to experimentally determined EPSA values. All these indexes were used to model the uptake
of drugs through the BBB. Highly significant statistical models (r2 (n−1)=0.81) were achieved by using WASA
and/or EPSA values along with other experimentally determined (e.g. phospholipophilicity) and in silico calculated
descriptors
Improving the performance of contemporary packed and open-tubular capillary electrochromatography
Get PDFCapillary electrochromatography (CEC) has been described as a highly efficient separation technique. However, after more then twenty years of research, industrial implementation is still not been reported. Restrictions in column technology and the limited robustness of the instrumentation hampered the evolution of CEC. In this thesis, kinetic plots for CEC is developed as a tool to evaluate the performance of contempoary commercial CEC and for the evaluation of new strategies to develop stationary phases in CEC
Kinetic-performance and selectivity optimization in supercritical fluid chromatography
Get PDFPacked-column supercritical fluid chromatography (pSFC) is known for several years to be a cheaper, greener, and/or faster alternative for LC for chiral and preparative separations. However, in the recent years, SFC has gained a renewed interest in the field of achiral analytical separations thanks to the innovations made in instrumental design. nevertheless, the use of the inherently compressible mobile phase in SFC still delivers some difficulties that are not present when performing LC separations. In this PhD research, it was shown that it is possible to deal with these difficulties when SFC performance is measured or in selectivity prediction of SFC separations
Supercritical fluid chromatography and enhanced fluidity liquid chromatography : green alternatives to conventional liquid chromatography
Get PDFThe growing interest in high throughput assays is the result of the increasing numbers and because of the growing complexity of samples to be analyzed in pharmaceutical environments. The low viscosities and high diffusivities of sub- and supercritical fluids allow highly efficient separations to be achieved with significant analysis time gains, in comparison to High-performance liquid chromatography (HPLC). In addition at the start of this research in 2009 there was a global shortage of acetonitrile, a solvent which is widely used in the pharmaceutical industry for the analysis of drug substances and drug products. As a consequence, seeking to use alternative solvents or analytical methods to minimize the impact of this shortage and its environmental impact was and is a contemporary highly relevant concern. CO2 is particularly attractive as an alternative mobile phase because of its green character and as it is easily brought under supercritical conditions (which are reaches at 31°C and 73.8 bar).
In chromatography liquid CO2 is therefore often used under sub- or supercritical as an extracting solvent and/or as the mobile phase with or without added organic modifier.
In the framework of the Pfizer Analytical Research Centre (PARC) and a general revival of SFC mainly because of the release of new instrumentation, SFC was critically re-evaluated in this study for analysis of achiral and chiral pharmaceuticals. In the same framework, EFLC was evaluated as the same instrumentation is used. Important in this evaluation is that ruggedness or robustness is taken into considerations because this is a prerequisite for a technique to recognize a breakthrough in a regulated environment such as the pharmaceutical industry. Evaluation in the SFC- and EFLC-mode of the recent developments made in LC related to column formats (porous particles, core shell particles, smaller particles, etc.) is included in this study
Hyphenating chromatographic, electrophoretic and on-line immobilized enzymatic strategies for improved oligonucleotide analysis
Get PDFMultidimensional and stationary-phase optimized selectivity strategies for improved chiral separation by fluid-based separation techniques
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Novel methods for quantitative drug metabolite profiling based on high performance liquid chromatography coupled to inductively coupled plasma - (tandem) mass spectrometry (HPLC-ICP-MS(/MS))
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