References of "Debrus, Benjamin"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailInnovative high-performance liquid chromatography method development for the screening of 19 antimalarial drugs based on a generic approach, using design of experiments, independent component analysis and design space
Debrus, Benjamin ULg; Lebrun, Pierre ULg; Mbinze Kindenge, Jérémie et al

in Journal of Chromatography. A (2011), 1218

An innovative methodology based on design of experiments (DoE), independent component analysis (ICA) and design space (DS) was developed in previous works and was tested out with a mixture of 19 ... [more ▼]

An innovative methodology based on design of experiments (DoE), independent component analysis (ICA) and design space (DS) was developed in previous works and was tested out with a mixture of 19 antimalarial drugs. This global LC method development methodology (i.e. DoE–ICA–DS) was used to optimize the separation of 19 antimalarial drugs to obtain a screening method. DoE–ICA–DS methodology is fully compliant with the current trend of quality by design. DoE was used to define the set of experiments to model the retention times at the beginning, the apex and the end of each peak. Furthermore, ICA was used to numerically separate coeluting peaks and estimate their unbiased retention times. Gradient time, temperature and pH were selected as the factors of a full factorial design. These retention times were modelled by stepwise multiple linear regressions. A recently introduced critical quality attribute, namely the separation criterion (S), was also used to assess the quality of separations rather than using the resolution. Furthermore, the resulting mathematical models were also studied from a chromatographic point of view to understand and investigate the chromatographic behaviour of each compound. Good adequacies were found between the mathematical models and the expected chromatographic behaviours predicted by chromatographic theory. Finally, focusing at quality risk management, the DS was computed as the multidimensional subspace where the probability for the separation criterion to lie in acceptance limits was higher than a defined quality level. The DS was computed propagating the prediction error from the modelled responses to the quality criterion using Monte Carlo simulations. DoE–ICA–DS allowed encountering optimal operating conditions to obtain a robust screening method for the 19 considered antimalarial drugs in the framework of the fight against counterfeit medicines. Moreover and only on the basis of the same data set, a dedicated method for the determination of three antimalarial compounds in a pharmaceutical formulation was optimized to demonstrate both the efficiency and flexibility of the methodology proposed in the present study. [less ▲]

Detailed reference viewed: 99 (36 ULg)
Full Text
Peer Reviewed
See detailApplication of a new optimization strategy for the separation of tertiary alkaloids extracted from Strychnos usambarensis leaves
Nistor, Iolanda ULg; Cao, Martine ULg; Debrus, Benjamin ULg et al

in Journal of Pharmaceutical & Biomedical Analysis (2011), 56

The HPLC separation of six alkaloids extracted from Strychnos usambarensis leaves has been developed and optimized by means of a powerful methodology for modelling chromatographic responses, based on ... [more ▼]

The HPLC separation of six alkaloids extracted from Strychnos usambarensis leaves has been developed and optimized by means of a powerful methodology for modelling chromatographic responses, based on three steps, i.e. design of experiments (DoE), independent component analysis (ICA) and design space (DS). This study was the first application of a new optimization strategy to a complex natural matrix. The compounds separated are the isomers isostrychnopentamine and strychnopentamine, 10-hydroxyusambarine and 11-hydroxyusambarine, also strychnophylline and strychnofoline. Three LC parameters have been optimized using a multifactorial design comprising 29 experiments that includes 2 center point replicates. The parameters were the percentage of organic modifiers used at the beginning of a gradient profile which consisted in different proportions of methanol (MeOH) and acetonitrile (MeCN), the gradient time to reach 70% of organic modifiers starting from the initial percentage and the percentage of MeCN found in the mobile phase. Subsequent to the experimental design application, predictive multilinear models were developed and used in order to provide optimal analytical conditions. The optimum assay conditions were: methanol/acetonitrile-sodium pentane sulfonate (pH 2.2; 7.5 mM) (33.4:66.6, v/v) at a mobile phase flow rate of 1mL/min during a 40.6 minutes gradient time. The initial organic phase contained 3.7% MeCN and 96.3% MeOH. The method showed good agreement between the experimental data and predictive value throughout the studied parameters space. Improvement of the analysis time and optimized separation for the compounds of interest was possible due to the original and powerful tools applied. Finally, this study permitted the acquisition of isomers profiles allowing the identification of the optimal collecting period of Strychnos usambarensis. [less ▲]

Detailed reference viewed: 84 (48 ULg)
Full Text
Peer Reviewed
See detailApplication of new methodologies based on design of experiments, independent component analysis and design space for robust optimization in liquid chromatography
Debrus, Benjamin ULg; Lebrun, Pierre ULg; Ceccato, Attilio ULg et al

in Analytica Chimica Acta (2011), 691

HPLC separations of an unknown sample mixture and a pharmaceutical formulation have been optimized using a recently developed chemometric methodology proposed by W. Dewé et al. in 2004 and improved by P ... [more ▼]

HPLC separations of an unknown sample mixture and a pharmaceutical formulation have been optimized using a recently developed chemometric methodology proposed by W. Dewé et al. in 2004 and improved by P. Lebrun et al. in 2008. This methodology is based on experimental designs which are used to model retention times of compounds of interest. Then, the prediction accuracy and the optimal separation robustness, including the uncertainty study, were evaluated. Finally, the design space (ICH Q8(R2) guideline) was computed as the probability for a criterion to lie in a selected range of acceptance. Furthermore, the chromatograms were automatically read. Peak detection and peak matching were carried out with a previously developed methodology using independent component analysis published by B. Debrus et al. in 2009. The present successful applications strengthen the high potential of these methodologies for the automated development of chromatographic methods. [less ▲]

Detailed reference viewed: 122 (41 ULg)
Full Text
See detailIntroduction à la chromatographie liquide
Debrus, Benjamin ULg; Hubert, Philippe ULg

Learning material (2011)

Detailed reference viewed: 124 (49 ULg)
Full Text
Peer Reviewed
See detailOptimisation and validation of a fast HPLC method for the quantification of sulindac and its related impurities
Krier, Fabrice ULg; Brion, Michaël; Debrus, Benjamin ULg et al

in Journal of Pharmaceutical & Biomedical Analysis (2011), 54

The European Pharmacopoeia describes a liquid chromatography (LC) method for the quantification of sulindac, using a quaternary mobile phase including chloroform and with a rather long run time. In the ... [more ▼]

The European Pharmacopoeia describes a liquid chromatography (LC) method for the quantification of sulindac, using a quaternary mobile phase including chloroform and with a rather long run time. In the present study, a new method using a short sub-2μm column, which can be used on a classical HPLC system, was developed. The new LC conditions (without chloroform) were optimised by means of a new methodology based on design of experiments in order to obtain an optimal separation. Four factors were studied: the duration of the initial isocratic step, the percentage of organic modifier at the beginning of the gradient, the percentage of organic modifier at the end of the gradient and the gradient time. The optimal condition allows the separation of sulindac and of its 3 related impurities in six minutes instead of 18 min. Finally, the method was successfully validated using an accuracy profile approach in order to demonstrate its ability to accurately quantify these compounds. [less ▲]

Detailed reference viewed: 155 (51 ULg)
Full Text
Peer Reviewed
See detailAnalytical tools to fight against counterfeit medicines
Marini Djang'Eing'A, Roland ULg; Mbinze Kindenge, J.; Montes, M. L. A. et al

in Chimica Oggi = Chemistry Today (2010), 28(5), 10-14

Counterfeiting has been dramatically increasing this last decade throughout the world and particularly in developing countries, with many consequences such as adverse impacts on public health, economics ... [more ▼]

Counterfeiting has been dramatically increasing this last decade throughout the world and particularly in developing countries, with many consequences such as adverse impacts on public health, economics and negative reputation for the pharmaceutical industry. Recognizing the magnitude of the issue, health authorities at national, regional and international levels are trying to fight against this scourge using various strategies including the setting-up of effective quality control that need to be reinforced through generic, fast and specific detection methods. To illustrate this topic, we will present several analytical tools, including liquid chromatography, low cost capillary electrophoresis and near infrared spectroscopy, developed and applied to the detection and quantification of counterfeit drugs. [less ▲]

Detailed reference viewed: 310 (71 ULg)
Full Text
Peer Reviewed
See detailTransfer of a conventional LC method for the screening of conterfeit antimalarial medicines to UHPLC
Nistor, Iolanda ULg; Lecomte, Frédéric ULg; Mbinze Kindenge, Jérémie et al

Poster (2010, September)

Detailed reference viewed: 120 (54 ULg)
Full Text
Peer Reviewed
See detailApplication of experimental design for the HPLC-UV-MS separation of aporphine alkaloids from leaves of Spirospermum Penduliflorum thouars
Rafamantanana, Mamy H.; Debrus, Benjamin ULg; Raoelison, Guy E. et al

Poster (2010, September)

Detailed reference viewed: 93 (13 ULg)
Full Text
Peer Reviewed
See detailOptimisation and validation of a fast HPLC method for the quantitation of sulindac and its impurities
Krier, Fabrice ULg; Brion, Michaël; Debrus, Benjamin ULg et al

Poster (2010, September)

Detailed reference viewed: 126 (43 ULg)
Full Text
Peer Reviewed
See detailContribution to fight against counterfeit medecines applying several analytical tools
Marini Djang'Eing'A, Roland ULg; Mbinze Kindenge, Jérémie; Montes, M. L. A. et al

Poster (2010, September)

Detailed reference viewed: 151 (46 ULg)
Full Text
Peer Reviewed
See detailA DESIGN SPACE APPROACH TO DEVELOP A GENERIC CE METHOD FOR THE SEPARATION OF 19 ANTIMALARIAL DRUGS
Lamalle, Caroline ULg; Marini Djang'Eing'A, Roland ULg; Debrus, Benjamin ULg et al

Poster (2010, September)

This project consists in analysing different molecules used against malaria by capillary electrophoresis (CE). As qualitative and quantitative counterfeit is largely present in Africa, it is important to ... [more ▼]

This project consists in analysing different molecules used against malaria by capillary electrophoresis (CE). As qualitative and quantitative counterfeit is largely present in Africa, it is important to develop a simple method which can control the conformity of medicines from African market. For the moment no CE method has been developed to analyse simultaneously the most common antipaludics; but it can be very useful for the control of unknown tablets. The method development was performed on 4 preservatives (methylparaben, propylparaben, butylhydroxyanisol and butylhydroxytoluen) and 16 antipaludics (artesunate, artemether, amodiaquine hydrochloride, chloroquine diphosphate, piperaquine, primaquine diphosphate, quinine hydrochloride, cinchonine, mefloquine hydrochloride, lumefantrine, halofantrine, sulfadoxine, sulfalen, atovaquone, proguanil hydrochloride, pyrimethamine). Micellar electrokinetic chromatography (MEKC) was chosen because of the presence of neutral and charged compounds in the studied mixture. The first step of method development was to screen CE experimental conditions to select the most crucial factors. Several conditions were tested with antipaludics diluted in 100% methanol and in 70:30 (v/v) methanol/water in which resolution was better. Four parameters as well as their investigation domain were then chosen: pH (5-10), SDS concentration (20-90nM), acetonitrile proportion (10-40%) and temperature (20-35°C). Then, in order to predict the best condition for the method, an experimental design methodology using a face-centered central composite design (CCD) was realised. Twenty five experiments were defined by CCD. Molecules were separated in four groups and each molecule could be found in two groups. Four samples containing 10 molecules were therefore injected to reduce the number of runs. All the results were analysed and allowed the prediction of optimal conditions in terms of analyte separation. Finally, the condition giving the best separation was tested to verify the prediction. [less ▲]

Detailed reference viewed: 68 (18 ULg)
Full Text
Peer Reviewed
See detailDosage des opiacés, cocaïne et amphéramines dans le sérum par UPLC/MSMS
Dubois, Nathalie ULg; Debrus, Benjamin ULg; Charlier, Corinne ULg

in Acta Clinica Belgica (2010), 65(1), 75-84

Detailed reference viewed: 122 (20 ULg)