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See detailComparing the qualitative performances of handheld NIR and Raman spectrophotometers for the detection of falsified pharmaceutical products
Ciza Hamuli, Patient ULiege; Sacre, Pierre-Yves ULiege; Waffo Tchounga, Christelle ULiege et al

in Talanta (2019), 202

Over the last decade, the growth of the global pharmaceutical market has led to an overall increase of substandard and falsified drugs especially on the African market (or emerging countries). Recently ... [more ▼]

Over the last decade, the growth of the global pharmaceutical market has led to an overall increase of substandard and falsified drugs especially on the African market (or emerging countries). Recently, several methods using handheld/portable vibrational spectroscopy have been developed for rapid and on-field drug analysis. The objective of this work was evaluate the performances of various NIR and Raman handheld spectrophotometers in specific brand identification of medicines through their primary packaging. Three groups of drug samples (artemether-lumefantrine, paracetamol, and ibuprofen) were used in tablet or capsule forms. In order to perform a critical comparison, the analytical performances of the two analytical systems was compared statistically using three methods: hierarchical clustering algorithm (HCA), data-driven soft independent modeling of class analogy (DD-SIMCA) and hit quality index (HQI). The overall results show good detection abilities for NIR systems compared to Raman systems based on Matthews’s correlation coefficients, generally close to one. Raman systems are less sensitive to the physical state of the samples than the NIR systems, it also suffers of the auto-fluorescence phenomenon and the signal of highly dosed active pharmaceutical ingredient (e.g. paracetamol or lumefantrine) may mask the signal of low-dosed and weaker Raman active compounds (e.g. artemether). Hence, Raman systems are less effective for specific product identification purposes but are interesting in the context of falsification because they allow a visual interpretation of the spectral signature (presence or absence of API). [less ▲]

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See detailSurface enhanced Raman imaging applied to quality control of solid dosage forms
Cailletaud, Johan ULiege; De Bleye, Charlotte ULiege; Gutt, Yoann et al

Conference (2019, June 25)

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See detailComparison of hyperspectral imaging techniques for the elucidation of falsified medicines composition
Coic, Laureen ULiege; Sacre, Pierre-Yves ULiege; Dispas, Amandine ULiege et al

in Talanta (2019), 198

Hyperspectral imaging has shown a high potential to analyze falsifications of solid pharmaceutical products since the last decade. Thanks to the non-destructive, ecological and non-invasive properties, it ... [more ▼]

Hyperspectral imaging has shown a high potential to analyze falsifications of solid pharmaceutical products since the last decade. Thanks to the non-destructive, ecological and non-invasive properties, it is a preferred technique for these kinds of applications. Moreover, thanks to the spectroscopic properties, it is possible to detect as well organic compounds as inorganic compounds in a single analysis. Therefore, we recommend using it as second-line laboratory analysis technique. Raman microscopy and Fourier Transform Infrared (FT-IR) microscopy are two interesting techniques that are complementary. In this study, the potential of the two hyperspectral imaging techniques is evaluated to elucidate the composition of falsified antimalarial tablets. Hyperspectral data are analyzed by Multivariate Curve Resolution-Alternating Least Square (MCR-ALS). The results obtained from this study show that Raman hyperspectral imaging seems to be more suited to detect low dosed compounds possibly due to a smallest sampling volume. It has been also possible to link formulations of falsified samples of two different brands. [less ▲]

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See detailQUALITATIVE AND QUANTITATIVE ANALYSIS OF N-GLYCANS PART OF PHARMACEUTICAL PROTEINS BY FT-IR SPECTROSCOPY
Hamla, Sabrina ULiege; Sacre, Pierre-Yves ULiege; Derenne, Allison et al

Conference (2019, May 20)

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See detailHANDHELD RAMAN SPECTROSCOPY: AN ESSENTIAL TOOL TO TACKLE THE SUBSTANDARD MEDICINES ISSUE?
Coic, Laureen ULiege; Sacre, Pierre-Yves ULiege; Dispas, Amandine ULiege et al

Conference (2019, May 20)

According to the World Health Organization, there is a growing concern about the quality of medicines around the world. Indeed, more and more substandard and falsified medicines are identified. That is ... [more ▼]

According to the World Health Organization, there is a growing concern about the quality of medicines around the world. Indeed, more and more substandard and falsified medicines are identified. That is why several spectroscopic techniques such as Raman, near- or mid-infrared spectroscopy, have gained great interest for this purpose. By means of chemometrics, interesting results have been shown in terms of elucidation of falsified medicines composition by hyperspectral imaging (L. Coic) and with benchtop spectrophotometers (O.Ye. Rodionova). However, these instruments are rather expensive, heavy and are not appropriated for low and middle-income countries. To circumvent these issues, several low-cost and middle-cost handheld spectrophotometers have been developed. In some cases of falsification, there is presence of a wrong or an absence of active pharmaceutical ingredient (API) that is often easy to prove with spectroscopy. However, the major part of the burden is constituted of lower dosed API that is trickier to evaluate in the field with conventional tools. In this study, the potential of handheld Raman spectroscopy to assay API in a solid dosage form was evaluated. For this purpose, fifteen formulations with a various proportion of mannitol and microcrystalline cellulose, seven level of concentration of ibuprofen (14 % – 26 % (m/m)) were produced thanks to a design of experiments, following the ICH Q3 guidelines. The calibration set was realized by analysing 3 tablets per formulation and each tablet was assayed using a previously validated benchtop NIR model. The PLS model was developed using PLS-Toolbox running in a Matlab® environment. The PLS model calibration has shown very nice results, with a R² of calibration / R² of cross-validation of 0.981 / 0.968 and a RMSECV of 0.83% (m/m). As explained, the validation set was projected on model and showed a RMSEP of 0.89 % (m/m). Then, the quantitative model has been validated following the total error approach with 4 series, 5 levels of concentration and 3 replicates. The acceptance limits were set at +/-15 % following the European Pharmacopeia criteria for uniformity of content. In a nutshell, handheld Raman spectrophotometer has shown very interesting results for studied formulation. Thanks to the 14 – 26 % (m/m) range, the model could be applied to get the quantitative information of the dosage of substandard medicines on the field. [less ▲]

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See detailPrinciples of Analytical Quality by Design for the development of quality control methods in a pharmaceutical context
Deidda, Riccardo ULiege; Avohou, Tonakpon Hermane ULiege; Jambo, Hugues ULiege et al

Conference (2019, May 20)

Pharmaceutical regulatory agencies increasingly require the implementation of systematic approaches covering the entire life-cycle of pharmaceutical products, from manufacturing processes to quality ... [more ▼]

Pharmaceutical regulatory agencies increasingly require the implementation of systematic approaches covering the entire life-cycle of pharmaceutical products, from manufacturing processes to quality control tests. In 2009, the International Council for Harmonisation (ICH) of technical requirements for pharmaceuticals for human use proposed a systematic approach named “Quality by Design” (QbD) to be implemented in the pharmaceutical field [1]. In this context, the QbD strategy have been progressively applied also to other aspects of the pharmaceutical chain, such as the analytical method development in quality control laboratories. The QbD applied to analytical chemistry is commonly named “Analytical Quality by Design” (AQbD) and in the last decade it has been widely applied in academia for the development of separation methods, involving different techniques such as LC, CE as well as SFC. However, its implementation in quality control laboratories still remains limited and then its advantages not completely exploited. Indeed, this approach presents a lot of conveniences, such as the deep knowledge acquired during the method development/optimisation by studying how critical method parameters (CMPs) affect critical method attributes (CMAs). Moreover, this strategy allows the possibility to define a method operable design region (MODR) consisting of a multitude of possible working points and for each of them a specific probability of success (π) is given. Indeed, the concept of risk plays a central role in this strategy as the MODR is considered of a zone of theoretical robustness limited by the so-called edges of failure, outside which the method performances are not accepted [2]. This presentation focuses first on the theoretical aspects regarding each step of this strategy. The analytical target profile definition, the selection of CMPs and CMAs, as well as screening and optimisation of CMPs and MODR definition are accurately described and illustrated. Some considerations about the choice of the working point, its validation and the planning of an efficient control strategy are also given. In the second part of this presentation all these concepts are once again showcased but from a practical point of view, by giving two concrete case-studies following the AQbD approach. The first one concerns the development of a liquid chromatography coupled to UV (LC-UV) method aimed at quantifying the cannabinoids content in cannabis extracts used for medicinal purposes [3]. The second one shows the approach applied to the development of a stability indicating method by using another analytical technique, the supercritical-fluid-chromatography coupled to mass spectrometry (SFC-MS). This latter is intended to be used for the quantification of hydro-soluble vitamins and amino acids in a complex medium. References [1] ICH Harmonised Tripartite guideline. Pharmaceutical Development Q8(R2) (2009) International Council for harmonisation of technical Requirements for Pharmaceutical for Human Use. [2] R. Deidda, S. Orlandini, Ph. Hubert, C. Hubert, Risk-based approach for method development in pharmaceutical quality control context: A critical review, J. Pharm. Biomed. Anal. 161 (2018) 110-121. [3] R. Deidda, H.T. Avohou, R. Baronti, P.L. Davolio, B. Pasquini, M. Del Bubba, C. Hubert, Ph. Hubert, S. Orlandini, S. Furlanetto, Analytical quality by design: Development and control strategy for a LC method to evaluate the cannabinoids content in cannabis olive oil extracts, J. Pharm. Biomed. Anal. 166 (2019) 326-335. [less ▲]

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See detailVibrational spectroscopy in analysis of pharmaceuticals: Critical review of innovative portable and handheld NIR and Raman spectrophotometers
Deidda, Riccardo ULiege; Sacre, Pierre-Yves ULiege; Clavaud, Matthieu et al

in TrAC: Trends in Analytical Chemistry (2019), 114

The fast pace of changes occurring in the pharmaceutical world emphasizes the need for powerful technologies that allow checking the quality of pharmaceutical products. Infrared and Raman spectroscopies ... [more ▼]

The fast pace of changes occurring in the pharmaceutical world emphasizes the need for powerful technologies that allow checking the quality of pharmaceutical products. Infrared and Raman spectroscopies have shown great potentialities for drug analysis in the last decades and consequently caught the attention of the scientific world as well as of industrial developers, leading to major technological advancements. These fast, eco-friendly, and non-destructive techniques help gather essential information about the samples under examination with consistent advantages. This review focuses on the application of portable/handheld NIR and Raman spectrophotometers in the analysis of pharmaceutical products for both in-process and quality control tests. Moreover, several analytical methods developed by several authors are described in order to illustrate the applications explored until now. [less ▲]

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See detailDéveloppement d’une méthode SFC-MS pour le dosage de vitamines en matrice complexe : Application de la stratégie « Analytical Quality by Design »
Deidda, Riccardo ULiege; Mignolet, Marie ULiege; Jambo, Hugues ULiege et al

Conference (2019, March 26)

Les agences réglementaires pharmaceutiques exigent de plus en plus fréquemment la mise en œuvre des approches systématiques couvrant l'ensemble du cycle de vie des produits pharmaceutiques, des processus ... [more ▼]

Les agences réglementaires pharmaceutiques exigent de plus en plus fréquemment la mise en œuvre des approches systématiques couvrant l'ensemble du cycle de vie des produits pharmaceutiques, des processus de fabrication jusqu’aux tests de contrôle qualité. En 2009, the International Council for Harmonisation of Technical Requirements for Pharmaceutical for Human Use (ICH) a proposé une approche systématique appelée « quality by design » appliqué à la production pharmaceutique. Ce concept étendu aux méthodes analytiques, « analytical quality by design (AQbD) », fait l’objet de recherches approfondies dans les milieux universitaires. Cette stratégie est appliquée aux méthodes séparatives telles que la LC, la CE et la SFC, mais reste actuellement relativement peu étendu au niveau des laboratoires de contrôle de qualité des industries pharmaceutiques. Pourtant, la stratégie AQbD présente un avantage considérable. En effet, elle permet d’obtenir une connaissance approfondie de la méthode et ce, tout au long du développement et de l’optimisation de celle-ci. L’évaluation des paramètres critiques de la méthode (CMPs) sur base de ses attributs critiques (CMAs) rend possible la définition d’une région opérationnelle probable (MODR). Cette région consiste en une multitude de conditions de travail possibles, où pour chacune d’elles, une probabilité de succès spécifique (π) est attribuée. En effet, la notion de risque joue un rôle primordial permettant ainsi d’assurer la robustesse de la méthode tout au long de son cycle de vie. Ce projet s'est concentré sur les aspects pratiques de cette stratégie en donnant un exemple concret de développement d'une méthode SFC-MS (entièrement conforme à la stratégie AQbD) pour une étude de stabilité d’une matrice complexe dans un contexte de contrôle de la qualité. Le développement de la méthode AQbD commence par la définition des requis analytiques (ATP), qui représentent l'objectif de la méthode dans le cadre de son utilisation spécifique. Dans ce cas-ci, l'échantillon étudié est constitué d'un milieu de culture cellulaire complexe constitué de plus de 40 composés et pour lequel les données relatives à la composition qualitative et quantitative ne sont pas complètement disponibles. Ensuite, plusieurs vitamines hydrophiles doivent être quantifiées afin de contrôler la stabilité de ce milieu. Dans la mesure où un effet matrice conséquent avait été mis en évidence dans une étude antérieure (UHPLC-MS), la chromatographie en phase supercritique couplée à la spectrométrie de masse a été choisie comme technique analytique alternative. En effet, dans certaines conditions, la SFC-MS peut être moins affectée par les effets de matrice que la LC-MS [3]. Afin de mettre en place correctement la stratégie AQbD, des expériences préliminaires ont été menées de manière rationnelle dans le but de sélectionner les meilleures conditions de départ. Dans cette phase, appelée « scouting », plusieurs phases stationnaires ont été testées et les colonnes les plus prometteuses ont été sélectionnées afin de mener des essais complémentaires. Différents gradients et modificateurs ont également été préalablement testés afin de sélectionner les conditions permettant l’élution des analytes d’intérêt. En effet, les vitamines ciblées présentent un comportement chromatographique varié entrainant des rétentions très différentes. Les critères de séparation et l'effet de matrice ont été étudiés et optimisés, en prenant en compte non seulement les aspects chromatographiques mais également ceux liés à la détection par MS. Dans ce contexte, une phase « screening » a été menée pour identifier les CMPs ayant une incidence importante sur les CMAs. Ensuite, les CMPs ont fait l’objet d’une étude approfondie au cours de la phase d’optimisation afin de mieux comprendre leur influence sur les performances de séparation et détection de la méthode. Cette dernière partie permettra d’introduire le concept de risque en appliquant des simulations de Monte-Carlo et une approche bayésienne capable d’évaluer l’incertitude du model proposé [4]. Par conséquent, une MODR liée à une probabilité de réussite définie, en termes de respect des spécifications données aux CMAs, sera obtenue. La MODR représente une zone de robustesse théorique dont chacun des points peut être sélectionné comme une condition opératoire en vue d’être validée. Cela démontre l'utilité de cette approche pour la mise au point d'une méthode analytique appliquée aux études de stabilité et ce, dans un contexte de contrôle de la qualité [2]. References [1] ICH Harmonised Tripartite guideline. Pharmaceutical Development Q8(R2) (2009) International Council for harmonisation of technical Requirements for Pharmaceutical for Human Use. [2] R. Deidda, S. Orlandini, Ph. Hubert, C. Hubert, Risk-based approach for method development in pharmaceutical quality control context: A critical review, J. Pharm. Biomed. Anal. 161 (2018) 110-121. [3] V. Desfontaine, F. Capetti, R. Nicoli, T. Kuuranne, J.-L. Veuthey, D. Guillarme, Systematic evaluation of matrix effects in supercritical fluid chromatography versus liquid chromatography coupled to mass spectrometry for biological samples, J. Chromatogr. B 1079 (2018) 51-61. [4] E. Rozet, P. Lebrun, Ph. Hubert, B. Debrus, B. Boulanger, Design Spaces for analytical methods, Trends Anal. Chem. 42 (2013) 157-167. [less ▲]

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See detailProcess Analysis - Overview
Ziemons, Eric ULiege; Hubert, Cédric ULiege; Hubert, Philippe ULiege

in Miro, Manuel; Worsfold, Paul; Townshend, Alan (Eds.) et al Encyclopedia of Analytical Science (2019)

Process analysis is the application of analytical science to the monitoring and control of industrial processes. The data obtained from process analysis allow the optimization, dynamic changes, monitoring ... [more ▼]

Process analysis is the application of analytical science to the monitoring and control of industrial processes. The data obtained from process analysis allow the optimization, dynamic changes, monitoring or quality control of industrial processes by providing information from which the chemical and/or physical composition of the process stream can be inferred. [less ▲]

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See detailProcess Analysis: Maintenance, Reliability, and Training
Hubert, Cédric ULiege; Widart, Joëlle ULiege; Ziemons, Eric ULiege et al

in Encyclopedia of Analytical Science 3rd Edition (2019)

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See detailOptimisation of a surface enhanced Raman scattering method using design of experiments and Bayesian design space modelling
Deidda, Riccardo ULiege; Avohou, Tonakpon Hermane ULiege; Kasemiire, Alice ULiege et al

Poster (2019, January 30)

Surface enhanced Raman scattering (SERS) is an alternative technique based on Raman spectroscopy, which has been increasingly applied to pharmaceutical analytical chemistry in the last decade. It consists ... [more ▼]

Surface enhanced Raman scattering (SERS) is an alternative technique based on Raman spectroscopy, which has been increasingly applied to pharmaceutical analytical chemistry in the last decade. It consists in enhancing the Raman effect by performing analyses using metallic surfaces, such as silver and gold colloids, on which the target molecules are adsorbed to be detected. It has been observed that in this way, an enhancement factor of 103-106 times can be obtained and the lack of sensibility related to conventional Raman scattering overcome [1]. Nowadays, design of experiment (DoE) is widely employed for modelling phenomena in analytical method development and optimisation, especially in the context of separation techniques. It is a structured approach that allows correlating key responses to controllable variables. Ideally, a certain number of factors may affect the critical method attributes (CMAs) of an analytical process in a negative or positive way. These factors are named critical method parameters (CMPs). DoE is employed, as a chemometric tool, to individuate CMPs and then, deeply study how they affect the process under study. To do so, CMAs are linked to CMPs by a regression model built by means of multivariate linear or partial least squares regression. Generally, the designs can be classified in two categories: screening and optimization designs. The formers are generally implemented when a high number of parameters are supposed to influence the analytical process and no much prior information is available. They result in useful tools to study the effects of both continuous and discontinuous factors. Instead, the optimisation designs are principally used to study wisely selected continuous factors [2]. The design space (DS) is defined as a multidimensional area in which the specifications given to the CMAs are met with a defined level of probability. Obviously, the larger the DS is, the more robust the method is. Its computation is achieved by several approaches, such as Monte-Carlo simulations, Bayesian methods as well as bootstrapping techniques [3]. The aim of this project was to combine and apply two potent chemometric tools such as DoE and Bayesian DS to SERS method development and optimisation. [1] Cailletaud, J., De Bleye, C., Dumont, E., Sacré, P.-Y., Netchacovitch, L., Gut, Y., Boiret, M., Ginot, Y.-M., Hubert, P., Ziemons, E., Critical review of surface-enhanced Raman spectroscopy applications in the pharmaceutical field. J. Pharm. Biomed. Anal. 147, 458-472, 2018. [2] Sahu, P.K., Ramisetti, N.R., Cecchi, T., Swain, S., Patro, C.S., Panda, J., An overview of experimental design in HPLC method development and validation, J. Pharm. Biomed. Anal. 147, 590-611, 2018. [3] Deidda, R., Orlandini, S., Hubert, P., Hubert, C., Risk-based approach for method development in pharmaceutical quality control context: A critical review. J. Pharm. Biomed. Anal. 161, 110-121, 2018. [less ▲]

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See detailAnalytical quality by design: development and control strategy for a LC method to evaluate the cannabinoids content in cannabis olive oil extracts
Deidda, Riccardo ULiege; Avohou, Tonakpon Hermane ULiege; Baronti, Roberto et al

in Journal of Pharmaceutical and Biomedical Analysis (2019)

Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) are considered as the most interesting cannabinoids in Cannabis sativa L. for the clinical practice. Since 2013, the Italian law allows pharmacists ... [more ▼]

Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) are considered as the most interesting cannabinoids in Cannabis sativa L. for the clinical practice. Since 2013, the Italian law allows pharmacists to prepare and dispense cannabis extracts to patients under medical prescription, and requires the evaluation of CBD and Δ9-THC content in cannabis extracts before sale. Cannabis olive oil extracts are prepared from dried female cannabis inflorescences, but a standard protocol is still missing. In this study, a fast RP-HPLC/UV method has been developed to quantify CBD and Δ9-THC in cannabis olive oil extracts. The analytical quality by design strategy has been applied to the method development, setting critical resolution and total analysis time as critical method attributes (CMAs), and selecting column temperature, buffer pH and flow rate as critical method parameters. Information from Doehlert Design in response surface methodology combined to Monte-Carlo simulations led to draw the risk of failure maps and to identify the method operable design region. The method was validated according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines and then implemented in routine analysis. A control strategy based on system control charts was planned to monitor the developed method performances. Evaluation data were recorded over a period of one year of routine use, and both the CMAs showed values within the specifications in every analysis performed. Hence, a new risk evaluation for the future performances of the method was achieved by using a Bayesian approach based on the routine use data, computing the future distribution of the two CMAs. Finally, a study focusing on the monitoring of CBD and Δ9-THC concentrations in cannabis olive oil extracts was carried out. The developed method was applied to 459 extracts. The statistical analysis of the obtained results highlighted a wide variability in terms of concentrations among different samples from the same starting typology of cannabis, underlining the compelling need of a standardised procedure to harmonise the preparation of the extracts. [less ▲]

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See detailUpdate of the progresses and development prospects of the FEDER project Phare
Emonts, Paul ULiege; Penoy, Noémie ULiege; Rocks, Natacha ULiege et al

Scientific conference (2019, January 19)

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See detailAuthentication of falsified medicine tablets by handheld Raman spectroscopy class modeling
Coic, Laureen ULiege; Sacre, Pierre-Yves ULiege; Avohou, Tonakpon Hermane ULiege et al

Conference (2019, January 01)

Since last decades, the world has known significant changes in the pharmaceutical products sale. The emergence of the internet trade is an important issue because it is easy to sell medicines without ... [more ▼]

Since last decades, the world has known significant changes in the pharmaceutical products sale. The emergence of the internet trade is an important issue because it is easy to sell medicines without passing any control. Moreover, in low- and middle-income countries (LMIC), the number of local pharmacies has grown, increasing the risk to have substandard or falsified medicines. Indeed, according to the World Health Organization (WHO) it is difficult to ensure quality medicines due to areas conflict, corrupted governments and poor health system [1]. For that reason, several analytical techniques have been developed since last decade. One of the most interesting tool is the Minilab, developed by the Global Pharma Health Fund (GPHF), which is a mobile mini-laboratory for fast drug quality control. Moreover, Raman spectroscopy has gained a great interest because it can be used at any step of analytical chain or on the fieldwork with handheld devices. However, spectroscopic data implies development of chemometrics models to gather relevant information. Several unsupervised techniques have already been used to authenticate drug products [2-3]. Due to the intrinsic properties of classification methods, class modeling is more appropriated to this kind of analysis. Indeed, falsified medicines can be quite different from the calibration set, so that, it does not have sense to attribute a class meanwhile it is dissimilar to the calibration set. In this study, the performances of two class-modeling techniques will be evaluated on handheld Raman spectra, to separate falsified medicines from authentic drugs. Three different generics of paracetamol, ibuprofen and artemether-lumefantrine with different dosage, dosage form and formulations were analyzed. Most of them were gathered in local Belgium pharmacies and other were gathered in Africa (artemether-lumefantrine formulations). Samples were analyzed with a handheld Raman spectrophotometer Pharma 21CFR part 11 qualified (Truscan RM, Thermo Scientific, USA) directly through the blister. In order to have a good representativeness of intra-batch variability, 10 tablets were analyzed per sample. The acquisition parameters were set to default. Two models were tested: one-class PLS (OC-PLS) [4] and the data driven-soft independent modeling class analogy (DD-SIMCA) [5]. All the computations were done in Matlab® (R2017b). The calibration and validation set was the same for each model and composed of 60 spectra for each, with different batch number. Because of the nature of each algorithm, there is a significant difference in terms of separation. Looking at Figure 1, the separation of dosage form for ibuprofen is much different between the two models. For the DD-SIMCA, it is more difficult to separate the long acting release from the soft capsule/coated tablet compared to the OC-PLS model. For the other API, similar results are obtained for the dosage and for the brand. It seems that the OC-PLS is more sensitive to the small spectral variabilities. In the case of artemether-lumefantrine formulations, the separation between samples is much more difficult. Indeed, the lumefantrine is a high Raman scatterer. This can explain that the signal of artemether and excipients is difficult to access. Elsewhere, in terms of development, the DD-SIMCA is much harder to optimize because there are more tunable parameters than for OC-PLS. Furthermore, both models are really influenced by spectral pretreatment. An optimization has to be done for each. The authentication of pharmaceutical products by handheld Raman spectroscopy has been possible thanks to class modeling. Both tested algorithms shown interesting results regarding the separation of samples depending on their characteristics. The optimization of data processing and pre-processing is the key-step to improve as sensitivity as specificity of both class modeling methods. [less ▲]

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See detailVibra-Santé Hub
De Bleye, Charlotte ULiege; Widart, Joëlle ULiege; Sacre, Pierre-Yves ULiege et al

Poster (2018, December 19)

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See detailDevelopment and optimization of a derivatization protocol for phenethylamine compounds using FITC-CE-LIF method
Emonts, Paul ULiege; Dispas, Amandine ULiege; Ninane, Caroline et al

Poster (2018, December 19)

In the framework of the development of an innovative microfluidic system based on capillary electrophoresis separation, we optimized a fluorescein isothiocyanate (FITC) derivatization protocol for Laser ... [more ▼]

In the framework of the development of an innovative microfluidic system based on capillary electrophoresis separation, we optimized a fluorescein isothiocyanate (FITC) derivatization protocol for Laser Induced Fluorescence (LIF) detection. The microfluidic device will present a high sensitivity thanks to the fluorescence detection and an innovative hydrodynamic injection approach. To highlight the analytical performances of this microfluidic system, we will use synthetic cathinones (and some derivatives) as targeted compounds. They present a panel of closely related structures and isobaric compounds. In addition to analytical challenges, this category of drugs is a current topic regarding to public health. Indeed synthetic cathinones were described as the second most frequently seized group of new psychoactive substances in EU in 2016. Moreover some of them are currently sell on internet as bath salts without any legislation. In this context, fast, easy and reliable analytical tools are required to track and quantify these compounds. In the present study, we initiated the optimization of the derivatization of model compounds (phenethylamine family) using FITC. The panel of model analytes includes primary and secondary amino groups to be representative of future real samples. Design of experiments strategy was used to optimize the derivatization protocol in order to reach an easy sample preparation and to maximize the derivatization efficiency. Finally, the CE developed method will be transferred to the microfluidic system. Then separation performances comparison of traditional CE-LIF vs µCE-LIF will allow to highlight the advantages of microfluidics such as the lower amount of sample required, the gain in time and money, the significant decrease of solvent and its compact size. [less ▲]

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See detailControl strategy applied to a LC-DAD quality control method as part of the analytical quality by design approach: one year of routine use
Deidda, Riccardo ULiege; Avohou, Tonakpon Hermane ULiege; Orlandini, Serena et al

Scientific conference (2018, December 19)

The analytical quality by design approach has been previously applied to the method development. The analytical target profile (ATP) was defined as the baseline separation of the two analytes of interest ... [more ▼]

The analytical quality by design approach has been previously applied to the method development. The analytical target profile (ATP) was defined as the baseline separation of the two analytes of interest, cannabidiol and Δ9-tetrahydrocannabinol. The critical method attributes (CMAs) were set as the critical resolution between a peak pair (Rs) and the analysis time (t). Critical method parameters were studied, and the response surface methodology was used to optimise the method. The method operable design region (MODR) was obtained by Monte-Carlo simulations and risk of failure maps setting the probability of meeting the specifications (Rs ≥ 0.85 and t ≤ 6 min) at 95%. A working point within the MODR was chosen, validated, and implemented in routine analyses. The information collected during the optimisation studies was conveyed to the planning of the control strategy consisting in system suitability test and control charts. The CMAs used for method optimisation were chosen as system suitability criteria to monitor the behaviour of the method performance. The evaluation was conducted over a period of one year of routine use. Both the CMAs showed values within the specifications in each analysis performed. On the basis of these results, a new and more complete risk evaluation was achieved. [less ▲]

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See detailDevelopment of graphical user interface (GUI) for database building and for falsification applications
Coic, Laureen ULiege; Sacre, Pierre-Yves ULiege; Dispas, Amandine ULiege et al

Scientific conference (2018, December 19)

Inside a research unit, there are several kind of information which are gathered in a continuous flow from operators. It is important to centralize all of the information not to lose any interesting ... [more ▼]

Inside a research unit, there are several kind of information which are gathered in a continuous flow from operators. It is important to centralize all of the information not to lose any interesting result. Because of the cost and/or the non-applicability of commercial database software, it is interesting to build its own one. Indeed, in the case of spectroscopic data, the use of a market database software is not user-friendly because, stored data cannot be directly manipulated in multivariate analyses applications. The database under development actually contains the data of various pharmaceutical samples (genuine and falsified) obtained on several spectroscopic devices. For this application, a Matlab® graphical user interface (GUI) is being developed. It provides the access to spectroscopic data for any operator and allows the automatic implementation of new instruments and/or new formulation groups. Moreover, in case of falsification suspicion, another GUI has been developed to provide qualitative information regarding the composition of the medicines. It is an interesting tool because it provides an instantaneously visual comparison between reference database and the unknown spectrum. Moreover, statistical tools, as Hit Quality Index or correlation coefficient, can provide a numerical result to quantify the match between spectra. In the future, results from other kind of techniques (e.g. HPLC, dissolution curves, photos) will be added to centralize samples information. [less ▲]

Detailed reference viewed: 26 (8 ULiège)