Espectroscopia aplicada

Scientific conference (2011, May)

Comment adéquatement déclarer valide ou non valide une méthode analytique ?

Conference (2011, April 04)

Vu le rôle central que jouent les méthodes d’analyse dans l’ensemble des activités tant de l’industrie (bio)pharmaceutique, agro-alimentaire, chimique ou dans l’environnement, il est essentiel de les ... [more ▼]

Vu le rôle central que jouent les méthodes d’analyse dans l’ensemble des activités tant de l’industrie (bio)pharmaceutique, agro-alimentaire, chimique ou dans l’environnement, il est essentiel de les valider. Les critères de validation ne sont pas une finalité et il est nécessaire de rappeler l’objectif d’une méthode analytique et de sa validation afin de planifier adéquatement cette étape de validation. Par ailleurs, les approches de décision habituelles qui se basent seulement sur des estimateurs ponctuelles ne répondent pas à l’objectif de la validation. Une stratégie alternative pour décider de la validité des méthodes est proposée utilisant les intervalles de tolérance : "ß-expectation tolerance interval". [less ▲]

Comparison between new and old excipients

Report (2011)

Design Space and desirability index. A Bayesian predictive risk-based approach to flexibly achieve multi-criteria decision methods.

Conference (2011, March 02)

The Design Space (DS) is defined as the set of factors settings (input conditions) that will provide results at least better than pre-defined acceptance limits. The proposed methodology aims at ... [more ▼]

The Design Space (DS) is defined as the set of factors settings (input conditions) that will provide results at least better than pre-defined acceptance limits. The proposed methodology aims at identifying a region in the space of factors that will likely provide satisfactory results during the future use of an analytical method or process in routine, through an optimization process. In a Bayesian framework, the responses are modelled using a multivariate multiple regression model allowing deriving their joint predictive posterior distribution. On the basis of this consequent distribution, a multi-criteria risk-based decision is taken with respect to the pre-defined acceptance limits. This aims to identify the DS. In this context, desirability methodologies are also applied to take the risk-based decision in a more flexible way. An example based on high-performance liquid chromatography illustrates the applicability of the methodology with highly correlated and constrained responses. [less ▲]

Contrôle qualité

Article for general public (2011)

Le fléau des faux médicaments

E-print/Working paper (2011)

The traffic in counterfeit medicines is booming. It misleads, and it kills. A University of Liège team is making Rwandan and Congolese health care workers aware of the problem, whilst informing and ... [more ▼]

The traffic in counterfeit medicines is booming. It misleads, and it kills. A University of Liège team is making Rwandan and Congolese health care workers aware of the problem, whilst informing and training them, so that they may detect and monitor these products, thanks to made to measure appropriate technical systems. [less ▲]

Validation, transfer and measurement uncertainty estimation of an HPLC-UV method for the quantification of artemisinin in hydro alcoholic extracts of Artemisia annua L.

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

Malaria is the world’s most important parasitic infection with 500 millions cases annually and almost 2 millions death per year. This disease is more present in Sub-Saharan Africa where 90% of the ... [more ▼]

Malaria is the world’s most important parasitic infection with 500 millions cases annually and almost 2 millions death per year. This disease is more present in Sub-Saharan Africa where 90% of the infections are found. Artemisinin and its semi synthetic derivatives (artemether, artesunate) have actually the most powerful activity on malaria, even in its complicated forms and resistance cases. Various methods have been proposed for detection and quantification of artemisinin in Artemisia annua L. by HPLC-UV, but the plant extracts used for this quantification were extracts obtained with organic solvents (toluene, petroleum ether, hexane …). To be able to use crude A. annua extracts prepared at low cost to formulate antipaludic drugs, we chose the use of a mixture of water and ethanol as solvent of extraction, but no adequate analytical method for this kind of extracts is published. The main objectives of this work were first to develop an analytical method for artemisinin quantification in hydro alcoholic extracts of A. annua. Second, this method had to be thoroughly validated by the research and development laboratory and, third, the transfer of this method to the routine laboratory had to be demonstrated. The final aim was to compare the estimation of measurement uncertainty obtained during the method validation with validation standards to measurement uncertainty estimates obtained during the method transfer study with real samples. The method was validated following the accuracy profile methodology and was found to be accurate in the concentration range of 10.0 to 54.0 µg/ml with CV <8%. Limit of detection and of quantification were 2.73 and 10.0 µg/ml, respectively. The method was then successfully transferred to a laboratory in Benin by showing that the quality of the results that it will generate during routine application of the method is sufficient. Finally, the measurement uncertainty of the method was estimated from the validation experiments as well as from the transfer study with authentic unspiked samples of A. annua. The comparison of these measurement uncertainty estimations showed that they were coherent. It confirmed thus that the estimation of measurement uncertainty from validation experiments predicts well the measurement uncertainty of real routine samples. This analytical method was thus shown to be convenient for routine analysis of hydro alcoholic extracts of A. annua in Benin. [less ▲]

Evaluating the reliability of analytical results using a probability criterion: a Bayesian perspective

in Analytica Chimica Acta (2011), 705

Methods validation is mandatory in order to assess the fitness of purpose of the developed analytical method. Of core importance at the end of the validation is the evaluation of the reliability of the ... [more ▼]

Methods validation is mandatory in order to assess the fitness of purpose of the developed analytical method. Of core importance at the end of the validation is the evaluation of the reliability of the individual results that will be generated during the routine application of the method. Regulatory guidelines provide a general framework to assess the validity of a method, but none address the issue of results reliability. In this study, a Bayesian approach is proposed to address this concern. Results reliability is defined here as “the probability of an analytical method to provide analytical results within predefined acceptance limits around their reference or conventional true concentration values over a defined concentration range and under given environmental and operating conditions.” By providing the minimum reliability probability needed for the subsequent routine application of the method, as well as specifications or acceptance limits , the proposed Bayesian approach provides the effective probability of obtaining reliable future analytical results over the whole concentration range investigated. This is summarized in a single graph: the reliability profile. This Bayesian reliability profile is also compared to two frequentist approaches, the first one derived from the work of Dewé et al. [Dewé W., Govaerts B., Boulanger B., Rozet E., Chiap P., Hubert Ph., Chemometr. Intell. Lab. Syst. 85 (2007) 262-268] and the second proposed by Govaerts et al. [B. Govaerts, W. Dewé, M. Maumy, B. Boulanger, Qual. Reliab. Engng. Int. 24 (2008) 667-680]. Furthermore, to illustrate the applicability of the Bayesian reliability profile, this approach is also applied here to a bioanalytical method dedicated to the determination of ketoglutaric acid (KG) and hydroxymethylfurfural (HMF) in human plasma by SPE-HPLC-UV. [less ▲]

Innovative 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

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 ▲]

Application of a new optimization strategy for the separation of tertiary alkaloids extracted from Strychnos usambarensis leaves

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 ▲]