Application of new methodologies based on design of experiments, independent component analysis and design space for robust optimization in liquid chromatography

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 ▲]

Optimisation and validation of a fast HPLC method for the quantification of sulindac and its related impurities

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 ▲]

Optimisation and validation of a fast HPLC method for the quantification of sulindac and its related impurities

Poster (2010, November 15)

Analytical tools to fight against counterfeit medicines

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 ▲]

Transfer of a conventional LC method for the screening of conterfeit antimalarial medicines to UHPLC

Poster (2010, September)

Application of experimental design for the HPLC-UV-MS separation of aporphine alkaloids from leaves of Spirospermum Penduliflorum thouars

Poster (2010, September)

Implementation of design space concept for the development of robust analytical methods

Poster (2010, September)

A DESIGN SPACE APPROACH TO DEVELOP A GENERIC CE METHOD FOR THE SEPARATION OF 19 ANTIMALARIAL DRUGS

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 ▲]

Development of robust analytical methods using design space methodology

Poster (2010)

Validated quantitative simultaneous determination of cocaine opiates and amphetamines in serum by U-HPLC coupled to tandem mass spectrometry

in Acta Clinica Belgica (2010), 65(Supplement 1),