References of "Caliaro, Gabriel"
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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 ▲]

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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 ▲]

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See detailA new statistical method for the automated detection of peaks in UV-DAD chromatograms of a sample mixture
Debrus, Benjamin ULg; Lebrun, Pierre ULg; Ceccato, Attilio ULg et al

in Talanta (2009), 79

One of the major issues within the context of the fully automated development of chromatographic methods consists of the automated detection and identification of peaks coming from complex samples such as ... [more ▼]

One of the major issues within the context of the fully automated development of chromatographic methods consists of the automated detection and identification of peaks coming from complex samples such as multi-component pharmaceutical formulations or stability studies of these formulations. The same problem can also occur with plant materials or biological matrices. This step is thus critical and time-consuming, especially when a Design of Experiments (DOE) approach is used to generate chromatograms. The use of DOE will often maximize the changes of the analytical conditions in order to explore an experimental domain. Unfortunately, this generally provides very different and “unpredictable” chromatograms which can be difficult to interpret, thus complicating peak detection and peak tracking (i.e. matching peaks among all the chromatograms). In this context, Independent Components Analysis (ICA), a new statistically based signal processing methods was investigated to solve this problem. The ICA principle assumes that the observed signal is the resultant of several phenomena (known as sources) and that all these sources are statistically independent. Under those assumptions, ICA is able to recover the sources which will have a high probability of representing the constitutive components of a chromatogram. In the present study, ICA was successfully applied for the first time to HPLC–UVDAD chromatograms and it was shown that ICA allows differentiation of noise and artifact components from those of interest by applying clustering methods based on high-order statistics computed on these components. Furthermore, on the basis of the described numerical strategy, itwas also possible to reconstruct a cleaned chromatogram with minimum influence of noise and baseline artifacts. This can present a significant advance towards the objective of providing helpful tools for the automated development of liquid chromatography (LC) methods. It seems that analytical investigations could be shortened when using this type of methodologies. [less ▲]

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See detailNouvelle méthodologie pour le développement automatisé de méthodes analytiques en chromatographie liquide pour l’analyse de mélanges de composés inconnus
Debrus, Benjamin ULg; Lebrun, Pierre ULg; Rozet, Eric ULg et al

in Spectra Analyse (2009), 268

Nowadays, many strategies to optimize chromatographic methods are available. However, the development of chromatographic methods remains the most limiting step in the process of synthesis or ... [more ▼]

Nowadays, many strategies to optimize chromatographic methods are available. However, the development of chromatographic methods remains the most limiting step in the process of synthesis or identification of new molecules that could lead to therapeutic agents or new biomarkers despite the availability of new technologies both in chemistry (chemical combinatorial, high throughput screening...) and in analytical biochemistr y (proteomics, metabolomics, herbal ... fingerprinting). Therefore, the aim of this study is to test a new methodology for developing automated chromatographic methods combining experimental planning, independent component analysis, analysis of predictive error propagation and multiple linear regression modeling. Finally, this automated methodology has enabled us to successfully separate the components of an unknown mixture. [less ▲]

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See detailDevelopment of a new predictive modelling technique to find with confidence equivalence zone and design space of chromatographic analytical methods
Lebrun, Pierre ULg; Govaerts, Bernadette; Debrus, Benjamin ULg et al

in Chemometrics and Intelligent Laboratory Systems (2008), 91

A new method for modelling chromatographic responses is presented as a critical piece for the achievement of automated development of analytical methods. This methodology is based on four parts. First, we ... [more ▼]

A new method for modelling chromatographic responses is presented as a critical piece for the achievement of automated development of analytical methods. This methodology is based on four parts. First, we propose to use a very little set of statistical equations to create predictive models for retention time based responses as the apex, the width and the asymmetry of peaks. Second, an experimental design is set up to realize experiments. Third, using grid search over the domain, multi criteria decision is taken with respect to different local or global optimization criteria, used as desirability functions. This allows finding an optimal chromatogram. Fourth, we advice to investigate how the predictive error of the models propagates around optimal solution. This allows to give confidence in the optimal solution, in finding a set of zones that presumably will give an acceptable solution. Design spaces can be derived with a similar technique. The approach is exemplified with a real case and predictions of models at optimal analytical conditions are validated through new experiments. Flexibility is left over all the presented methodology. [less ▲]

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