Biomedical subjects

Yvan Vander Heyden

Publications and source records attributed to Yvan Vander Heyden.

30 records · Page 2Linked to original sources

PubMed2004

Application of tetraoxadiaza-crown ether derivatives as chiral selector modifiers in capillary electrophoresis.

Two new diaza-crown ether derivatives (R-1, RS-1) have been synthesized from 1,4,10,13-tetraoxa-7,16-diazacyclooctadecane and tested as potential chiral selectors in capillary electrophoresis (CE) for the chiral separation of five amino acid derivatives. The individual use of the selectors did not lead to chiral differentiation. However, they enhanced the enantioselective effect of different cyclodextrins in dual selector systems. In this paper, we report the effect of different substituted diaza-crown ether derivatives on the separation results obtained in dual systems with cyclodextrins.

Amino Acids↗

PubMed2004

Characterisation of reversed-phase liquid-chromatographic columns by chromatographic tests comparing column classification based on chromatographic parameters and column performance for the separation of acetylsalicylic acid and related compounds.

Selection of RP-LC columns with suitable selectivity for a given analysis is difficult. For example, the European Pharmacopoeia (Ph. Eur.) and other official compendia for drug analysis only give a general description of the stationary phase in the operating procedure of a liquid chromatographic method. The need for a general test method to characterise RP-LC columns has been rising since the 1970s. A project to define a chromatographic procedure characterising RP-LC columns was started earlier. A procedure to measure test parameters was introduced and a classification of the columns, based on a minimal number of parameters, was obtained. This paper focuses on correlating the column classification with the selectivity obtained for a real separation. The separation of acetylsalicylic acid (aspirin) and related compounds was performed according to the Ph. Eur. monograph on the stationary phases previously characterised chromatographically. It was examined whether the classes of columns, determined using test parameter results, contain either suitable or unsuitable supports for the aspirin separation. The system suitability test prescribed by the Ph. Eur. in order to distinguish between suitable or unsuitable columns for this separation was also evaluated.

Aspirin↗

PubMed2004

Enantioseparations by capillary electro-chromatography: differences exhibited by normal- and reversed-phase versions of polysaccharide stationary phases.

The influence of using normal-phase and reversed-phase versions of four commercial polysaccharide stationary phases on chiral separations was investigated with capillary electrochromatography (CEC). Both versions of the stationary phases, Chiralcel OD, OJ, and Chiralpak AD, AS were tested for the separation of two basic, two acidic, a bifunctional, and a neutral compound. Different background electrolytes were used, two at low pH for the acid, bifunctional and neutral substances, and three at high pH for the basic, bifunctional and neutral ones. This setup allowed evaluating differences between both stationary-phase versions and between mobile-phase compositions on a chiral separation. Duplicate CEC columns of each stationary phase were in-house prepared and tested, giving information about the intercolumn reproducibility. In general, reversed-phase versions of the current commercial polysaccharide stationary phases are found to be best for reversed-phase CEC, even though at high pH no significant differences were seen between both versions. Most differences were observed at low pH. For acidic compounds, it was seen that an ammonium formate electrolyte performed best, which is also an excellent electrolyte if coupling with mass spectrometry is desired. For basic, bifunctional and neutral compounds, no significant differences between the three tested electrolytes were observed at high pH. Here, a phosphate buffer is preferred as electrolyte because of its buffering capacities. However, if coupling to mass spectrometry is wanted, the more volatile ammonium bicarbonate electrolyte can be used as an alternative.

Amylose↗

PubMed2003

Characterisation of reversed-phase liquid chromatographic columns by chromatographic tests. Rational column classification by a minimal number of column test parameters.

The European Pharmacopoeia (Ph. Eur.) and other official compendia give only a general description of the stationary phase in the description of a liquid chromatographic method. Therefore the selection of a column giving suitable selectivity presents difficulties. Earlier, a test procedure was proposed that allows to measure 36 chromatographic parameters which have been described for characterising stationary phases. This procedure was carried out on 69 reversed-phase liquid chromatography (RP-LC) columns. This paper focuses on the classification of RP-LC stationary phases based on chromatographic parameters. A chemometric study was conducted using 24 parameters that could be measured in a repeatable and reproducible way. Principal component analysis was used to classify the columns and to estimate the minimal number of parameters necessary for a rational classification. It is shown that after reducing the number of parameters from 24 to four or three, similar classifications were obtained. The column classifications were compared to the European Pharmacopoeia stationary phase description and to the column properties obtained from the manufacturers.

Chromatography, Liquid↗

PubMed2003

Robustness testing of chiral separations by capillary electrophoresis using highly-sulfated cyclodextrins.

The robustness of a generic method for chiral separation in capillary electrophoresis using highly-sulfated cyclodextrins in a low pH phosphate buffer and the "short-end injection technique" was studied. In this study, we focused on the robustness of the separations and not of the quantitative analysis of the enantiomers. The robustness was evaluated for the enantiomeric separation of a basic (propranolol), a neutral (praziquantel) and an acidic (warfarin) compound. The influence of eight factors which were believed to affect significantly the separations was studied using a 11-factor, 12-experiment Plackett-design. Statistical interpretation of the factor effects on different analytical responses (selectivity and resolution) was performed. The separations of the three compounds could be considered as rather robust as the factor effects were generally not significant (alpha = 0.05) and small.

Cyclodextrins↗

PubMed2003

Influence of peak measurement parameters on the quality of chiral electrophoretic separations.

The effect of nine peak measurement/analysis parameters on chiral capillary electrophoresis (CE), followed by UV detection, was studied. The parameters pertained UV-detection (detection wavelength, reference wavelength, and wavelength bandwidths), signal processing (data acquisition rate, type and amount of filtering) and peak detection (detection threshold and peak width). The influence of these factors on the chiral separation of dimethindene enantiomers was studied at two different concentrations (i.e., at high and low signal-to-noise (S/N) ratio) by the means of experimental designs. The electropherogram characteristics considered were the resolution between the two enantiomers, the peak areas, and the S/N ratio. A D-optimal design was first used as screening design to identify the most critical parameters. Afterwards, a modelling of the different responses as a function of these critical parameters was performed based on the results of a face-centered central composite design. The results showed that the signal-processing parameters should be carefully selected when developing a CE separation since very important variations in the separation, the S/N ratio and the peak area of the substances can occur by setting these parameters at different levels. The detection wavelength should also be carefully chosen for optimal peak area measurement. The role of these parameters becomes more important with decreasing concentration of the analytes (i.e., low S/N ratio). This study showed that the peak measurement/analysis parameters should be optimized as the chemical and physical parameters of a method. They also should always be well specified in order to allow a good transfer of a method from one instrument to another.

Electrophoresis, Capillary↗

PubMed2003

Enantioseparations of basic and bifunctional pharmaceuticals by capillary electrochromatography using polysaccharide stationary phases.

A fast screening strategy was developed in capillary electrochromatography (CEC) for the chiral separation of basic and bifunctional compounds. The screening conditions were determined on polysaccharide chiral stationary phases using 15 pharmaceutical compounds. The content and type of organic modifier, as well as the pH of the mobile phase appeared to have the largest influence on the chiral resolution. It was seen that for acidic compounds, our approach was not suitable. A generic mobile phase for basic and bifunctional compounds was determined. The testing on 20 additional compounds showed that the proposed mobile phase performed well since enantioselectivity was observed for 86% of the investigated compounds. A comparison of CEC and reversed-phase liquid chromatography (RPLC) results was attempted to demonstrate the potential of the used technique for chiral method development.

Chromatography↗

PubMed2002

Characterisation of reversed-phase liquid chromatographic columns by chromatographic tests. Evaluation of 36 test parameters: repeatability, reproducibility and correlation.

The European Pharmacopoeia (Ph. Eur.) or other official compendia give only a general description of the stationary phase in the description of a liquid chromatographic method. Therefore the selection of a column giving suitable selectivity presents difficulties. Earlier, a test procedure was proposed that allows measurement of a number of parameters which are reported to be representative for stationary phase characteristics. This paper describes how the test procedure was applied on 69 RP-LC C18 columns. Chromatographic parameters obtained as test results were evaluated, and their repeatability, reproducibility and correlation were examined.

Chromatography, High Pressure Liquid↗

PubMed2002

Derivation of system suitability test limits from a robustness test on an LC assay with complex antibiotic samples.

A System Suitability Test (SST) is a test to verify the adequate working of the equipment used for analytical measurements. In pharmaceutical analysis, SSTs are performed at least at the beginning of a series of routine analyses. The most generally applied SST considers the precision of the analysis, i.e. the repeatability standard deviation must not exceed a predefined value. Additionally, a SST can also consider responses indicative for the quality of the technique used, e.g. resolutions between peaks or peak asymmetry in high performance liquid chromatography. The system is then only declared suitable if the response is within given limits. However, it is not always evident how to define the SST limits to be fulfilled for a newly developed method. Robustness tests have been proposed as a starting point in a strategy to deduce these limits. Here, it is examined how such a strategy can be applied for complex samples of microbial origin.

Anti-Bacterial Agents↗

PubMed2002

Minimal number of chromatographic test parameters for the characterisation of reversed-phase liquid chromatographic stationary phases.

This paper focuses on the classification or differentiation of RP-HPLC columns based on measured chromatographic properties. A chemometric study has been conducted on a published data set consisting of 85 RP-HPLC columns and on a data set consisting of 47 self-tested columns. Principal component analysis enables determination of the number of parameters necessary for a rational differentiation. The results show that reducing the number of parameters for such differentiation still allows classification of the columns just as a higher number did. It is shown that three test parameters produce a classification similar to that obtained with five parameters.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

Classification tree models for the prediction of blood-brain barrier passage of drugs.

The use of classification trees for modeling and predicting the passage of molecules through the blood-brain barrier was evaluated. The models were built and evaluated using a data set of 147 molecules extracted from the literature. In the first step, single classification trees were built and evaluated for their predictive abilities. In the second step, attempts were made to improve the predictive abilities using a set of 150 classification trees in a boosting approach. Two boosting algorithms, discrete and real adaptive boosting, were used and compared. High-predictive classification trees were obtained for the data set used, and the models could be improved with boosting. In the context of this research, discrete adaptive boosting gives slightly better results than real adaptive boosting.

Blood-Brain Barrier↗

PubMedDate not supplied

Prediction of peptide retention at different HPLC conditions from multiple linear regression models.

To quantitatively characterize the structure of a peptide and to predict its gradient retention time at given HPLC conditions three structural descriptors are used: (i) logarithm of the sum of retention times of the amino acids composing the peptide, log SumAA, (ii) logarithm of the van der Waals volume of the peptide, log VDW(Vol), (iii) and the logarithm of the peptide's calculated n-octanol-water partition coefficient, clog P. The log SumAA descriptor is obtained from empirical data for 20 natural amino acids, determined in a given HPLC system. The two other descriptors are calculated from the peptides' structural formulas using molecular modeling methods. The quantitative structure-retention relationships (QSRR), build by multiple linear regression, describe HPLC retention of peptide on a given chromatographic system on which the retention of the 20 amino acids was predetermined. A structurally diversified series of 98 peptides was employed. The predicted gradient retention times on several chromatographic systems were in good agreement with the experimental data. The QSRR equations, derived for a given system operated at variable gradient times and temperatures allowed for the prediction of peptide retention in that system. Matching the experimental HPLC retention to the theoretically predicted for a presumed peptide could facilitate original protein identification in proteomics. In conjunction with MS data, prediction of the retention time for a given peptide might be used to improve the confidence of peptide identifications and to increase the number of correctly identified peptides.

Amino Acid Sequence↗