References of "Hubert, Philippe"
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See detailDetermination of 4-aminophenol in a pharmaceutical formulation using Surface Enhanced Raman scattering: from development to method validation
De Bleye, Charlotte ULg; Dumont, Elodie ULg; Rozet, Eric ULg et al

in Talanta (2013), 116

A Surface Enhanced Raman Scattering (SERS) method able to quantify 4-aminophenol in a pharmaceutical formulation based on acetaminophen, also called paracetamol, was developed and, for the first time ... [more ▼]

A Surface Enhanced Raman Scattering (SERS) method able to quantify 4-aminophenol in a pharmaceutical formulation based on acetaminophen, also called paracetamol, was developed and, for the first time, successfully validated. In this context, silver nanoparticles were synthesized according to the method described by Lee-Meisel and used as SERS substrate. The repeatability of the silver colloid synthesis was tested using different methods to characterise the size and the zeta potential of silver nanoparticles freshly synthesized. To optimize the SERS samples preparation, a design of experiments implicating concentrations of citrate-reduced silver nanoparticles and aggregating agent was performed in order to maximize the Raman signal enhancement. Finally, an approach based on tolerance intervals and accuracy profiles was applied in order to thoroughly validate the method in a range of concentrations comprised from 3 to 15 µg mL-1 using normalized band intensities. The standard addition method was selected as method calibration. Therefore, measurements were carried out on 4-aminophenol spiked solutions of the pharmaceutical formulation. Despite the well-known stability and reproducibility problems of SERS, the validation was performed using two operators and 5 batches of nanoparticles, one for each validation day. [less ▲]

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See detailValidation data treatment
Marini Djang'Eing'A, Roland ULg; Rozet, Eric ULg; Hubert, Philippe ULg

Learning material (2013)

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See detailApplication of an innovative design space optimization strategy to thedevelopment of LC methods for the simultaneous screening of antibiotics to combat poor quality medicines
Mbinze Kindenge, Jérémie ULg; Dispas, Amandine ULg; Lebrun, Pierre ULg et al

in Journal of Pharmaceutical & Biomedical Analysis (2013), 85

The poor quality of medicines is a crucial problem of public health. Therefore, it is important to haveanalytical tools to attend decisions of the legal authorities while combating this offense. In this ... [more ▼]

The poor quality of medicines is a crucial problem of public health. Therefore, it is important to haveanalytical tools to attend decisions of the legal authorities while combating this offense. In this context,the main objective of this study was to develop generic methods able to trace, screen and determineseveral antibiotics and common associated molecules by mean of liquid chromatographic techniques.For that purpose, an innovative Design Space optimization strategy was applied, targeting 16 antibioticsand 3 beta-lactamase inhibitors. The robustness of the developed method allowed using its use in anenvironment where operational factors such as temperature are not easy to control and eased its trans-fer to Ultra High Performance Liquid Chromatography. To demonstrate its ability to quantify the targetedmolecules, the developed and transferred method was fully validated for two active ingredients com-monly used in association, sulbactam and ceftriaxone, using the accuracy profile as decision tool. Basedon this successful step, the method was then used for the quantitative determination of these two activeingredients in three pharmaceutical brands marketed in the Democratic Republic of Congo. Two out ofthe three pharmaceutical products did not comply with the specifications [less ▲]

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See detailDevelopment and validation of a UHPLC−LTQ−Orbitrap MS method for non-anthocyanin flavonoids quantification in Euterpe oleracea juice
Dias, A.L.; Rozet, Eric ULg; Larondelle, Y. et al

in Analytical and Bioanalytical Chemistry (2013)

Euterpe oleracea fruits have gained much attention because of their phenolic constituents that have shown potential beneficial effects for health. The aim of this work was to identify and quantify major ... [more ▼]

Euterpe oleracea fruits have gained much attention because of their phenolic constituents that have shown potential beneficial effects for health. The aim of this work was to identify and quantify major non-anthocyanin flavonoids in fruit juice by an accurate UHPLC−LTQ−Orbitrap MS method. Fruits were processed to juice, lyophilized and defatted. The residue was then extracted with methanol by sonication and the extraction time optimized giving recovery rates > 90%. Solubilization of dried extract was realized using 40% MeOH which showed the best compromise for MS detection. For the UHPLC quantification, a HSS C18 column (1.8µm) was used with a gradient elution of methanol and water both with 0.1% formic acid. Total error and accuracy profiles were used as validation criteria. Seven compounds and their isomers were successfully separated, including the major non-anthocyanin flavonoids. Calibration in the matrix was found to be more accurate than calibration without matrix. Trueness (< 15% relative bias), repeatability and intermediate precision (<13% RSD), selectivity, response function, linearity, LOD (ranged from 0.04 to 0.81 µg/mL) and LOQ (0.15 - 5.78 µg/mL) for 12 compounds were evaluated and the quantification method validated. Its applicability was demonstrated on real samples from different suppliers. Their qualitative and quantitative profiles were similar and some compounds were for the first time quantified. In addition eriodictyol was identified for the first time in this fruit along with 5 other flavonoids for which we proposed a possible structure. [less ▲]

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See detailDevelopment of a quantitative approach based on surface-enhanced Raman chemical imaging (SER-CI)
De Bleye, Charlotte ULg; Sacre, Pierre-Yves ULg; Dumont, Elodie ULg et al

Conference (2013, October 17)

During the last decade, Raman imaging has taken an important place in the pharmaceutical field [1-2]. It enables to acquire a visual representation of samples while quantifying and identifying molecules ... [more ▼]

During the last decade, Raman imaging has taken an important place in the pharmaceutical field [1-2]. It enables to acquire a visual representation of samples while quantifying and identifying molecules of these samples. However, this technique suffers from a lack of sensitivity and the appearance of fluorescence which can limit its pharmaceutical applications. One way to circumvent these limitations is Surface Enhanced Raman chemical imaging (SER-CI) which presents the advantages of Raman imaging and enables to dramatically increase the Raman scattering of molecules adsorbed or very close to metallic surfaces [3]. The number of publications regarding SER-CI in the pharmaceutical field is very limited probably due to the well-known stability and reproducibility problem of SERS and also due to the difficulty to obtain a homogeneous colloids covering of samples surface before SER-CI analyses. In this context, the possibility to develop a quantitative approach using SER-CI on a pharmaceutical model, presented as paracetamol tablet, was studied. The aim was to develop a SER-CI method enabling to quantify 4-aminophenol (4-AP), which is the main impurity of paracetamol actively research for its toxicity, at a concentration below its limit of specification of 1000 ppm [4]. This pharmaceutical model was first investigated using SERS and a quantitative method enabling to quantify 4-AP from 3 to 15 µg mL-1 was developed and validated [5]. Based on these previous results, the possibility to develop quantitative approach to quantify 4-aminophenol in paracetamol tablet using SER-CI was investigated. Different ways to cover the tablets surface by silver colloids were tested and a homogeneity study was performed in order to improve the repeatability of SER-CI analyses. Afterwards, the SER-CI approach was optimized and different spectral intensity normalizations were tested. Finally, a quantitative approach using SER-CI was developed enabling to quantify 4-AP from 0.025% to 0.2% (w/w) in paracetamol tablets. [less ▲]

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See detailRobust SFC method optimization using design space strategy
Dispas, Amandine ULg; Lebrun, Pierre ULg; Hubert, Philippe ULg

Conference (2013, October)

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See detailVibrational spectroscopy as PAT compliant tools
Ziemons, Eric ULg; De Bleye, Charlotte ULg; Chavez, Pierre-François ULg et al

Scientific conference (2013, September 10)

In the last decades, intensive research and development dealing with NIR and Raman spectroscopy have taken place in industrial field, espacially in pharmaceutical industry. This enthusiasm can be ... [more ▼]

In the last decades, intensive research and development dealing with NIR and Raman spectroscopy have taken place in industrial field, espacially in pharmaceutical industry. This enthusiasm can be explained by the fact that this technique are regarded as promising and attractive tools in PAT, R&D and Green Chemistry frameworks. Their advantages such as non-invasive, non-destructive, fast data acquisition, minization of sample preparation step and the use of probes in on-line, in-line and at-line are expected to reach the aims of PAT, R&D and Green Chemistry. [less ▲]

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See detailFast method for the simultaneous quantification of toxic polyphenols applied to the selection of genotypes of yam bean (Pachyrhizus sp.) seeds.
Lautié, Emmanuelle; Rozet, Eric ULg; Hubert, Philippe ULg et al

in Talanta (2013), 117

The purpose of the research was to develop and validate a rapid quantification method able to screen many samples of yam bean seeds to determine the content of two toxic polyphenols, namely pachyrrhizine ... [more ▼]

The purpose of the research was to develop and validate a rapid quantification method able to screen many samples of yam bean seeds to determine the content of two toxic polyphenols, namely pachyrrhizine and rotenone. The analytical procedure described is based on the use of an internal standard (dihydrorotenone) and is divided in three steps: microwave assisted extraction, purification by solid phase extraction and assay by ultra high performance liquid chromatography (UHPLC). Each step was included in the validation protocol and the accuracy profiles methodology was used to fully validate the method. The method was fully validated between 0.25mg and 5mg pachyrrhizin per gram of seeds and between 0.58mg/g and 4mg/g for rotenone. More than one hundred samples from different accessions, locations of growth and harvest dates were screened. Pachyrrhizine concentrations ranged from 3.29mg/g to lower than 0.25mg/g while rotenone concentrations ranged from 3.53mg/g to lower than 0.58mg/g. This screening along with principal component analysis (PCA) and discriminant analysis (DA) analyses allowed the selection of the more interesting genotypes in terms of low concentrations of these two toxic polyphenols. [less ▲]

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See detailA new criterion to assess distributional homogeneity in hyperspectral images of solid pharmaceutical dosage forms
Sacre, Pierre-Yves ULg; Lebrun, Pierre ULg; Chavez, Pierre-François ULg et al

Conference (2013, September)

During galenic formulation development, homogeneity of distribution is a critical parameter to check since it may influence activity and safety of the drug. Several techniques exist to assess this ... [more ▼]

During galenic formulation development, homogeneity of distribution is a critical parameter to check since it may influence activity and safety of the drug. Several techniques exist to assess this homogeneity, the most used and recognized being HPLC. However, these techniques are destructive, time consuming and uses a lot of organic solvents. Vibrational spectroscopies are promising green chemistry techniques that may replace HPLC for several analysis tasks thanks of their rapid, non-destructive and non-pollutant characteristics. Raman hyperspectral imaging is a technique of choice for assessing the distributional homogeneity of compounds of interest. Indeed, the combination of both spectroscopic and spatial information provides a detailed knowledge of chemical composition and component distribution. When dealing with hyperspectral imaging, multivariate data analysis is necessary to extract the concentration map of the compound of interest that will be used to assess sample homogeneity. Actually, most authors assess homogeneity using parameters of the histogram of intensities (e.g. mean, skewness and kurtosis). However, this approach does not take into account spatial information and loses the main advantage of imaging. Recently, Rosas et al. proposed a homogeneity index based on the Poole index. However, it necessitates cutting the maps in non-overlapping macropixels and is therefore quickly limited with small maps. To overcome this limitation, we propose a new criterion that combines Continuous Level Moving Blocks and homogeneity curves with a randomization step to assess the distributional homogeneity. This distributional homogeneity index (DHI) enables analysis of hyperspectral maps without apriori knowledge. It has been applied on five pharmaceutical formulations with different blending conditions. The uniformity content values of the API (present at a concentration of 7% w/w) measured by HPLC ranged from RSD: 0.46% to 11.04%. Ten tablets per formulation have been mapped over a region of interest of 4 mm². After extracting pure spectra by MCR-ALS, the concentration maps of the API were computed using classical least squares analysis. DHI have been computed with a hundred simulations for the randomization step for each concentration map. Afterwards, a mean DHI and standard deviation values were computed per formulation. A linear relationship has been observed between the RSD values and the mean DHI. These results enabled us to select the formulation with the best homogeneity. Further experiments are in progress to check whether hyperspectral imaging combined with DHI could be used in routine to assess blending homogeneity of well-known formulations. [less ▲]

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See detailChimie Analytique - Manuel de Travaux Pratiques
Dispas, Amandine ULg; Ziemons, Eric ULg; Hubert, Philippe ULg

Learning material (2013)

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See detailAnalyzing spectral data for the selection of a calibration model
Ziemons, Eric ULg; Moonen, François; Hubert, Philippe ULg

Patent (2013)

The invention relates to method of analyzing spectral data for the selection of a calibration model, relating spectra of a substance to physical or chemical parameter of the substance, over a ... [more ▼]

The invention relates to method of analyzing spectral data for the selection of a calibration model, relating spectra of a substance to physical or chemical parameter of the substance, over a predetermined range of the physical or chemical parameter. [less ▲]

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See detailChemical imaging of small molecules from simple to complex matrices: Quantitative approaches based on Surface Enhanced Raman scattering
De Bleye, Charlotte ULg; Sacre, Pierre-Yves ULg; Chavez, Pierre-François ULg et al

Conference (2013, July)

Surface Enhanced Raman scattering (SERS) allows to dramatically exalt the Raman diffusion of molecules absorbed or very closed to rough metallic surfaces while keeping their structural information. SERS ... [more ▼]

Surface Enhanced Raman scattering (SERS) allows to dramatically exalt the Raman diffusion of molecules absorbed or very closed to rough metallic surfaces while keeping their structural information. SERS chemical imaging, presenting a high specificity and sensibility, allows acquiring a visual representation of samples combining spectral and spatial measurements. This technique could become a powerful tool in pharmaceutical and biological analysis enabling to identify and quantify molecules thanks to chemometric evaluation while looking at their distribution or their interactions. In this context, SERS chemical imaging is investigated in detection or quantitative determination of molecules in pharmaceutical and biological matrices. The feasibility of making quantitative measurements using SERS is evaluated on small target molecules models such as 4-aminophenol and lactate. Firstly, a SERS method to quantify 4-aminophenol which is the primary impurity of acetaminophen coming from its degradation during the storage or from its synthesis was developed on a real pharmaceutical formulation. The standard addition method was selected as calibration method in order to take into account the matrix effect coming from the different components of the latter. Despite the well-known stability and repeatability problems of SERS, the method was thoroughly validated by means of accuracy profiles as decision tool. Moreover, this validation methodology allowed to define a first estimation of the real analytical performance of the technique. Secondly, the detection of lactate, which is a critical metabolite implicated in several metabolic disorders, was successfully tested in the physiological concentration in a simple matrix. Preliminary results for the determination of this metabolic biomarker were also very promising allowing to consider more complex matrices. Based on these results, SERS chemical imaging was implemented to detect 4-aminophenol in a pharmaceutical tablet formerly pulverised by a SERS substrate. Through this imaging technique, it was not only possible to detect the presence of the impurity at the limit of specification of 0.1% (w/w) but it was also possible to differentiate tablets comprising different concentrations of the latter. These promising results represent the first step towards quantitative measurements using SERS chemical imaging. [less ▲]

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See detailA New Method for Quality by Design Robust Optimization in Liquid Chromatography
Debrus, Benjamin ULg; Lebrun, Pierre ULg; Rozet, Eric ULg et al

in LC-GC Europe (2013), -(-), -

A new method to optimize liquid chromatography (LC) methods using a Quality by Design (QbD) approach is presented. This method is based on the use of design of experiments (DOE) and independent component ... [more ▼]

A new method to optimize liquid chromatography (LC) methods using a Quality by Design (QbD) approach is presented. This method is based on the use of design of experiments (DOE) and independent component analysis (ICA) to accurately estimate the modelled responses (that is, the retention times at the beginning, the apex, and the end) of each peak, even for coeluted peaks. The modelling of these responses usesmultiple linear regressions, while the propagation of the error affecting the responses and coming from the models is carried out by Monte Carlo simulation. The design space is determined as the region of assay factors where the probability to reach baseline-resolved peaks is higher than the desired level of quality. This method was applied to the optimization of the separation of nine compounds in a mixture, yielding the design space and the demonstration of robustness of the method. Finally, the method was validated. [less ▲]

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