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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 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 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 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 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 ▲]

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See detailSFC-MS for the quality control of cannabis: addressing the potential adulteration with synthetic cannabinoids
Jambo, Hugues ULiege; Dispas, Amandine ULiege; Avohou, Tonakpon Hermane ULiege et al

Scientific conference (2018, December 19)

Recent years have been the stage to a shift in cannabis policies and trends that have impacted cannabis usage and public perception. On the other hand, there has also been a rise in the development and ... [more ▼]

Recent years have been the stage to a shift in cannabis policies and trends that have impacted cannabis usage and public perception. On the other hand, there has also been a rise in the development and distribution of synthetic cannabinoids which are synthetic compounds that also act on the endocannabinoid receptors. They are mostly used as recreational drugs and because their potency and toxicity are not always known, they can lead to severe adverse effects after consumption. The detection of cannabis counterfeiting with synthetic cannabinoids is essential to produce safe cannabis-based medicines and we aimed to develop a generic supercritical fluid chromatography hyphenated to mass spectrometry (SFC-MS) method that could help in detecting such adulterations using representative synthetic cannabinoids from multiple classes. Method development started with a screening of stationary phases using seven different SFC-dedicated columns. Then, an optimization following analytical quality-by-design principles was performed followed by an assessment of the quantitative performances with a validation according to the total-error strategy. This innovative tool should prove useful in the context of counterfeit drugs tracking in the challenges to come. [less ▲]

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See detailFirst inter-laboratory study of a Supercritical Fluid Chromatography method for the determination of pharmaceutical impurities
Dispas, Amandine ULiege; Marini Djang'Eing'A, Roland ULiege; Desfontaine, Vincent et al

in Journal of Pharmaceutical and Biomedical Analysis (2018), 161

Supercritical Fluid Chromatography (SFC) has known a strong regain of interest for the last 10 years, especially in the field of pharmaceutical analysis. Besides the development and validation of the SFC ... [more ▼]

Supercritical Fluid Chromatography (SFC) has known a strong regain of interest for the last 10 years, especially in the field of pharmaceutical analysis. Besides the development and validation of the SFC method in one individual laboratory, it is also important to demonstrate its applicability and transferability to various laboratories around the world. Therefore, an inter-laboratory study was conducted and published for the first time in SFC, to assess method reproducibility, and evaluate whether this chromatographic technique could become a reference method for quality control (QC) laboratories. This study involved 19 participating laboratories from 4 continents and 9 different countries. It included 5 academic groups, 3 demonstration laboratories at analytical instrument companies, 10 pharmaceutical companies and 1 food company. In the initial analysis of the study results, consistencies within- and between-laboratories were deeply examined. In the subsequent analysis, the method reproducibility was estimated taking into account variances in replicates, between-days and between-laboratories. The results obtained were compared with the literature values for liquid chromatography (LC) in the context of impurities determination. Repeatability and reproducibility variances were found to be similar or better than those described for LC methods, and highlighted the adequacy of the SFC method for QC analyses. The results demonstrated the excellent and robust quantitative performance of SFC. Consequently, this complementary technique is recognized on equal merit to other chromatographic techniques. [less ▲]

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See detailSFC-MS as a preventive tool for the quality control of potentially adulterated cannabis with synthetic cannabinoids
Jambo, Hugues ULiege; Dispas, Amandine ULiege; Avohou, Tonakpon Hermane ULiege et al

Conference (2018, October 19)

Recent years have been the stage to a shift in cannabis policies and trends that have impacted cannabis usage and public perception. It has also caught the attention of the pharmaceutical industry and ... [more ▼]

Recent years have been the stage to a shift in cannabis policies and trends that have impacted cannabis usage and public perception. It has also caught the attention of the pharmaceutical industry and cannabis is increasingly evaluated as a medicine in the treatment of various conditions. On the other hand, there has also been a rise in the development and distribution of synthetic cannabinoids which are synthetic compounds that have the same pharmacological action as the natural cannabinoids found in the plant. They are mostly used as recreational drugs and because their potency and toxicity are not always known, they can lead to severe adverse effects after consumption. The detection of counterfeiting cannabis with synthetic cannabinoids is essential to produce safe cannabis-based medicines. Our aim was to develop a generic supercritical fluid chromatography hyphenated to mass spectrometry (SFC-MS) method that could help in detecting such adulterations using representative synthetic cannabinoids from multiple classes. Method development started with a screening of stationary phases using seven different SFC-dedicated columns. The Torus 1-AA (amino-anthracene) provided the best retention and resolution for the analytes and was selected for the study. Likewise, the mobile phase modifier composition (methanol/water 98:2 v/v) was set after these preliminary tests. The next step performed was the optimization of the method using a design of experiments (DoE) and Bayesian design space (DS) methodology. The temperature, pressure, isocratic and gradient time were selected as parameters for the DoE (central composite design). The separation criterion (S) was set to -0.5 to maximize the separation capacity of the generic method. This Quality by Design (QbD) approach is advantageous as it permits the testing of various conditions within the design space (DS) to achieve a desirable separation since unassessed compounds will probably be encountered during routine analysis. Finally, the quantitative performances were demonstrated by means method validation based on total error approach for the quantification of a selected synthetic cannabinoid in fiber type cannabis plant matrix. Sample preparation was performed with solid-liquid extraction (SLE) followed by filtration and dilution. The acceptance limits were set at ±15% and the β-expectation tolerance limits at 90 % probability level. The results show that the method is valid over the whole dosing range assessed of 2.5 - 7.5% (w/w) with the LOD equal to 14.40 ng/mL. The implementation of this method should be straightforward considering the ease of sample preparation, the use of a fast and green SFC separation and the high specificity and sensitivity achieved with mass spectrometry. Ensuring medicinal cannabis quality is challenging and this work adds an innovative tool that should prove useful in the context of counterfeit drugs tracking. [less ▲]

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See detailThe use of SFC from research and development to quality control laboratories: dream or reality?
Guillarme, Davy; Dispas, Amandine ULiege; Desfontaine, Vincent et al

Conference (2018, October)

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See detailTerahertz hyper-spectral imaging of lab-prepared versus commercial paracetamol tablets and potential applications
Nguyen, Thi Dinh; Dortu, Fabian; Dispas, Amandine ULiege et al

in Proceedings of SPIE : The International Society for Optical Engineering (2018, May 28), 1067731

Terahertz spectroscopy and imaging have proved to be a versatile tool for the studying of drugs and pharmaceutical analysis. Particularly, this method has been employed to map the coating layer of ... [more ▼]

Terahertz spectroscopy and imaging have proved to be a versatile tool for the studying of drugs and pharmaceutical analysis. Particularly, this method has been employed to map the coating layer of pharmaceutical tablets, to identify the polymorphism of active pharmaceutical ingredients (APIs), etc. In this paper, Terahertz (THz) hyper-spectral imaging using time-domain spectroscopy technique has been applied to image a commercial packaging of paracetamol tablets, showing the ability to penetrate through both cardboard of the box and plastic cover of the blister pack. The advantage of THz time-domain spectroscopy (THz-TDS) is that not only the dimensional imaging was captured but also the spectral information was registered. A comparison between THz spectrum of commercial and lab-prepared paracetamol tablets shows the presence of a certain amount of α-D-lactose monohydrate at the absorption peak of 0.53 THz. Any API or excipients can be detected if their fingerprints fall in the measureable range of the system. This work opens up a possibility of using THz-TDS to non-destructively control the quality of pharmaceutical products while they are still in their packaging. This potential capacity is important as for the identification of the APIs as well as changing of unwanted physical (and hence biological) properties during the shelf-life of the product. [less ▲]

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See detailTerahertz hyperspectral imaging of lab-prepared versus commercial paracetamol tablets and potential applications
Nguyen, Dinh; Dortu, Fabian; Dispas, Amandine ULiege et al

Poster (2018, April 25)

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See detail‘Quality by Design’ approach for the analysis of impurities in pharmaceutical drug products and drug substances
Dispas, Amandine ULiege; Avohou, Tonakpon Hermane ULiege; Lebrun, Pierre ULiege et al

in TrAC: Trends in Analytical Chemistry (2018), 101

The pharmaceutical industry is highly regulated by quality policies. The concept of risk management is strongly integrated into the quality assurance system to ensure pharmaceuticals’ quality and ... [more ▼]

The pharmaceutical industry is highly regulated by quality policies. The concept of risk management is strongly integrated into the quality assurance system to ensure pharmaceuticals’ quality and patients’ safety. In the context of quality control, the detection of impurities in raw materials and finished products is a major concern. It can be challenging for analytical scientists to meet specificity/selectivity and sensitivity requirements. Obviously, separation techniques are widely used for the detection of impurities but the method development required to achieve Analytical Target Profile (ATP) concerns is often challenging. Therefore, to ensure pragmatic and systematic methods development and simultaneously manage the risk associated with analytical methods, the principles of Quality by Design (QbD) should be applied. This paper provides an overview of QbD principles and statistical strategies (mainly DoE-DS approach) which can be applied to impurity detection methods, as well as a review of the literature where QbD has been applied to these types of analytical methods. [less ▲]

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See detailSupercritical fluid chromatography: a promising alternative to current bioanalytical techniques
Dispas, Amandine ULiege; Jambo, Hugues ULiege; André, Sébastien ULiege et al

in Bioanalysis (2018), 10(2), 107-124

During the last years, chemistry was involved in the worldwide effort toward environmental problems leading to the birth of green chemistry. In this context, green analytical tools were developed as ... [more ▼]

During the last years, chemistry was involved in the worldwide effort toward environmental problems leading to the birth of green chemistry. In this context, green analytical tools were developed as modern Supercritical Fluid Chromatography in the field of separative techniques. This chromatographic technique knew resurgence a few years ago, thanks to its high efficiency, fastness and robustness of new generation equipment. These advantages and its easy hyphenation to MS fulfill the requirements of bioanalysis regarding separation capacity and high throughput. In the present paper, the technical aspects focused on bioanalysis specifications will be detailed followed by a critical review of bioanalytical supercritical fluid chromatography methods published in the literature. [less ▲]

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See detailQuality control of medicinal cannabis: implementation of a generic sfc-ms method to address counterfeiting with synthetic cannabinoids
Jambo, Hugues ULiege; Dispas, Amandine ULiege; Avohou, Tonakpon Hermane ULiege et al

Poster (2018)

There is a growing interest in using cannabis for medicinal purposes as research shows evidence of its therapeutic properties. However, to be successfully ported in the pharmaceutical field, several ... [more ▼]

There is a growing interest in using cannabis for medicinal purposes as research shows evidence of its therapeutic properties. However, to be successfully ported in the pharmaceutical field, several aspects such as its quality must be evaluated and ensured. In this context, we address the possibility of counterfeiting of cannabis with synthetic cannabinoids and report the development of a robust method based on supercritical fluid chromatography coupled with mass spectrometry (SFC-MS) that could help in detecting such adulterations. Considering the high number of already available synthetic cannabinoids and the high rate of development of novel structures, we aimed to develop a generic method suitable for the analysis of a large panel of substances using seventeen synthetic cannabinoids from multiple classes as model compounds. Firstly, a suitable column was chosen after a screening phase. The mobile phase (modifier composition) was also set after these preliminary tests. Secondly, a method optimization was carried out using a design of experiments (DoE) and Bayesian design space (DS) methodology that follows ICH Q8 R2 guideline recommendations. This approach is increasingly recommended for the robust optimization of analytical methods. The DoE selected was a four-factor central composite design. Then, according to the goal of adequately analyzing future unknown compounds, the criterion separation S was set to -0.5 to obtain a method with the highest separation capacity. This quality by design (QbD) approach shows flexibility as it permits the testing of various conditions within the DS to tune the separation taking into account that some adaptations might be needed during routine analysis, since it is impossible to predict which compound will be found. Finally, the quantitative performances of the method were demonstrated by means of a validation step based on total error approach for the quantification of a selected synthetic cannabinoid in fiber type cannabis plant matrix. Sample preparation was performed with solid-liquid extraction (SLE) followed by filtration and dilution. The acceptance limits were set at ±15% and the β- expectation tolerance limits at 90 % probability level. The results show that the method is valid over the whole dosing range assessed of 2.5 - 7.5% (w/w) and the LOD equal to 14.40 ng/mL. The implementation of this method should be straightforward considering the ease of sample preparation, the use of a simple modifier composition and the high specificity and sensitivity achieved with mass spectrometry. This work adds an innovative tool to address the challenges of ensuring medicinal cannabis quality and will prove useful in the context of counterfeit drugs tracking. [less ▲]

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See detailImplementation of a generic SFC-MS method for the quality control of potentially counterfeited medicinal cannabis with synthetic cannabinoids
Jambo, Hugues ULiege; Dispas, Amandine ULiege; Avohou, Tonakpon Hermane ULiege et al

in Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences (2018), 1092

In this study, we describe the development of a SFC-MS method for the quality control of cannabis plants that could be potentially adulterated with synthetic cannabinoids. Considering the high number of ... [more ▼]

In this study, we describe the development of a SFC-MS method for the quality control of cannabis plants that could be potentially adulterated with synthetic cannabinoids. Considering the high number of already available synthetic cannabinoids and the high rate of development of novel structures, we aimed to develop a generic method suitable for the analysis of a large panel of substances using seventeen synthetic cannabinoids from multiple classes as model compounds. Firstly, a suitable column was chosen after a screening phase. Secondly, optimal operating conditions were obtained following a robust optimization strategy based on a design of ex- periments and design space methodology (DoE-DS). Finally, the quantitative performances of the method were assessed with a validation according to the total error approach. The developed method has a run time of 9.4 min. It uses a simple modifier composition of methanol with 2% H2O and requires minimal sample pre- paration. It can chromatographically separate natural cannabinoids (except THC-A and CBD-A) from the syn- thetics assessed. Also, the use of mass spectrometry provides sensitivity and specificity. Moreover, this quality by design (QbD) approach permits the tuning of the method (within the DS) during routine analysis to achieve a desirable separation since the future compounds that should be analyzed could be unknown. The method was validated for the quantitation of a selected synthetic cannabinoid in fiber-type cannabis matrix over the range of 2.5% – 7.5% (w/w) with LOD value as low as 14.4 ng/mL. This generic method should be easy to implement in customs or QC laboratories in the context of counterfeit drugs tracking. [less ▲]

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See detailIs supercritical fluid chromatography hyphenated to massspectrometry suitable for the quality control of vitamin D3 oilyformulations?
Andri, Bertyl ULiege; Dispas, Amandine ULiege; Klinkenberg, Régis et al

in Journal of Chromatography. A (2017), 1515

Nowadays, many efforts are devoted to improve analytical methods regarding efficiency, analysis timeand greenness. In this context, Supercritical Fluid Chromatography (SFC) is often regarded as a ... [more ▼]

Nowadays, many efforts are devoted to improve analytical methods regarding efficiency, analysis timeand greenness. In this context, Supercritical Fluid Chromatography (SFC) is often regarded as a goodalternative over Normal Phase Liquid Chromatography (NPLC). Indeed, modern SFC separations arefast, efficient with suitable quantitative performances. Moreover, the hyphenation of SFC to mass spec-trometry (MS) provides additional gains in specificity and sensitivity. The present work aims at thedetermination of vitamin D3 by SFC-MS for routine Quality Control (QC) of medicines specifically. Basedon the chromatographic parameters previously defined in SFC-UV by Design of Experiments (DoE) andDesign Space methodology, the method was adapted to work under isopycnic conditions ensuring a base-line separation of the compounds. Afterwards, the response provided by the MS detector was optimizedby means of DoE methodology associated to desirability functions. Using these optimal MS parameters,quantitative performances of the SFC-MS method were challenged by means of total error approachmethod validation. The resulting accuracy profile demonstrated the full validity of the SFC-MS method. It was indeed possible to meet the specification established by the European Medicines Agency (EMA) (i.e. 95.0 − 105.0% of the API content) for a dosing range corresponding to at least 70.0-130.0% of theAPI content. These results highlight the possibility to use SFC-MS for the QC of medicine and obviouslysupport the switch to greener analytical methods. [less ▲]

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