Reliable low cost capillary electrophoresis device for drug quality control and counterfeit medicines

in Journal of Pharmaceutical & Biomedical Analysis (2010), 53(5), 1278-1287

The proportion of counterfeit medicines is dramatically increasing these last few years. According to numerous official sources, in some pharmaceutical wholesalers in African countries, the proportion has ... [more ▼]

The proportion of counterfeit medicines is dramatically increasing these last few years. According to numerous official sources, in some pharmaceutical wholesalers in African countries, the proportion has reached 80%. Unfortunately, this situation is far to be improved due to lack of suitable analytical equipment allowing rapid actions of the Regulatory Agencies based on scientific consideration, at affordable cost and all over the drug supply chain. For that purpose, a network group considered that mater by building a low-cost original capillary electrophoresis (CE) equipment equipped with a new deep UV detector based on LED technology. The generic conditions for analysis were investigated: capillary zone electrophoresis (CZE) performed at acidic pH for basic drug molecules (i.e., quinine, highly used as the last antimalarial rampart), basic pH for compounds such as furosemide (a common diuretic drug) and at neutral pH for a well known antibiotic combination, trimethoprim/sulfamethoxazol. To evaluate the ability of the CE equipment for quantification, a full validation and a method comparison study were carried out for the CZE method dedicated to quinine determination. The validation involved the use of accuracy profile and total error concept to monitor the adequacy of the results obtained by the new prototype. The method comparison was based on the Bland and Altman approach by comparing results obtained by the low-cost CE and a conventional set-up. Subsequent validation studies were realized with neutral and acidic drug molecules, each focusing on a single concentration level calibration curve in order to maintain as low as possible the expenses due to reagents and thus the cost of analysis, as important advantages of CE for drug quality control. [less ▲]

Plans expérimentaux

Learning material (2010)

Vidéos du cours intitulé "Plans expérimentaux"

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

Poster (2010, September)

Total error as natural decision criteria for analytical methods validation and transfer

Conference (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 ▲]

Nettoyage des équipements et validation de nettoyage

Learning material (2010)

Contribution au développement des capacités d’enseignement et de formation pour l’amélioration de la qualité du médicament (acronyme : DEV-AQM)

Report (2010)

Audits de qualités des fournisseurs de produits pharmaceutiques: Aspects théoriques et pratiques

Learning material (2010)

Vidéo du cours intitulé "Audits de qualités des fournisseurs de produits pharmaceutiques: Aspects théoriques et pratiques".

Contribution au développement des capacités d’enseignement et de formation pour l’amélioration de la qualité du médicament (acronyme : DEV-AQM)

Report (2009)

Modèles statistiques Bayésiens et méthodologies pour calculer le Design Space (OPTIMAL-DS)

Report (2009)

La compréhension des procédés technologiques et industriels dans les secteurs (bio)pharmaceutiques, biotechnologiques, agroalimentaires et environnementaux doit permettre de se conformer aux lignes de ... [more ▼]

La compréhension des procédés technologiques et industriels dans les secteurs (bio)pharmaceutiques, biotechnologiques, agroalimentaires et environnementaux doit permettre de se conformer aux lignes de conduites initiées par la FDA ou d'autres organismes de contrôles. Notamment, le document ICH Q8 introduit les notions de "Process Analytical Technology", de "Quality by Design" et de "Design Space", ayant attraits à la qualité des procédés industriels, des procédés d'analyse ainsi qu'à la qualité des produits finis. Cependant, si les lignes de conduites pour ces exigences sont expliquées, aucune méthodologie pour les atteindre n'est donnée. Or, un nombre considérable de nouvelles entités chimiques sont synthétisées par les laboratoires pharmaceutiques, biotechnologiques ou agroalimentaires. Les producteurs de matières premières et/ou d’excipients (secteur chimique) ont également besoin de disposer rapidement de méthodes analytiques de contrôle qui leur permettront de s’assurer de la qualité de leurs produits. On comprend aisément la nécessité pour ces secteurs de disposer rapidement de résultats fiables puisque les activités de recherches mais aussi des investissements, souvent importants, sont orientés ou stoppés sur base de données chiffrées, produits par les méthodes analytiques. La production de résultats fiables et la démonstration de cette fiabilité sont donc économiquement fondamentales. Ce projet vise la mise au point de stratégies et de modèles génériques de développement automatisé de nouvelles méthodes analytiques séparatives, en se basant sur la modélisation des temps de rétention, la planification expérimentale, et le concept de Design Space. L’objectif connexe est d’appliquer cette méthodologie à l’optimisation de n’importe quel procédé. Le fait de pouvoir disposer d’une méthodologie de mise au point automatique de méthodes analytiques ou de tous procédés analytiques aura un impact significatif. Cette nouvelle technologie permettra de réduire de façon drastique le temps d’optimisation des méthodes et procédés, permettant une production plus efficiente de produits (pharmaceutique, cosmétique, agro-alimentaire ou biotechnologique) répondant aux spécifications du client. [less ▲]