Le déploiement d’outils de Contrôle de Qualité Analytique (CQA) intégrés à la boucle de soins apparaît comme un fort contributeur à la sécurisation du circuit des médicaments cytotoxiques en milieu de soin. Les techniques analytiques actuellement disponibles ont en commun d’être intrusives, de détruire une fraction des solutions thérapeutiques, d’exposer les personnels et de générer une filière spécifique d’élimination de déchets toxiques. En regard, de ces éléments, l’analyse non intrusive par Spectroscopie Raman (SR) est particulièrement innovante et en capacité d’améliorer significativement le cahier des charges technique du CQA. Le but de ce travail de thèse a été de procéder à une qualification opérationnelle de la SR dans le contexte du CQA hospitalier. Une attention particulière a été portée à la praticabilité de la nouvelle solution technique par SR, à son impact sur la sécurité et sur la sûreté des personnes et des biens ainsi qu’en terme environnemental. / The development of effective tools for the analytical quality control (AQC) of therapeutic objects (TO) appear to be a strong contributor to security of the cytotoxic drugs circuit in health care settings. Our goal is to ensure a high and stable quality in our pharmaceutical preparations for the benefit of patients and caregivers. Presently available analytical techniques have in common to be intrusive, destroying a fraction therapeutic solutions, exposing personal and generate specific toxic waste disposal. Compared to these, the non-intrusive analysis by Raman spectroscopy (RS) appears to us particularly innovative and has the capacity to significantly improve the specification of AQC technical specifications. The purpose of this work was to conduct an operational qualification of RS in the context of AQC. Special attention has been given to the feasibility of the new technical solution for SR, its impact on safety of persons and their working environment.

[pt] Um método analítico simples e verde para a quantificação dos teores de óleos essenciais de laranja doce e lavanda em blends foi desenvolvido utilizando a primeira derivada dos espectros de fluorescência sincronizada com preparação de amostras por microemulsões sem surfactante. Os pares de comprimentos de onda de excitação e emissão (Medições de absorvância no comprimento de onda de excitação/Medições de absorvância no comprimento de onda de emissão) foram determinados para ambos os óleos essenciais (336/436 nm para laranja doce e a 330/388 nm para lavanda). A otimização univariada foi conduzida para estabelecer as condições de preparo para os sistemas microemulsionados: 50 μL de fase oleosa contendo óleo essencial diluído em octan-1-ol (1:4, v/v), 2,0 mL de água e propan-1-ol até o volume final de 5,0 mL. Diferentes proporções de óleo essencial na fase oleosa foram preparadas para a construção das curvas analíticas a fim de monitorar a sensibilidade das curvas. Medições de fluorescência síncrona foram realizadas e os dados adquiridos foram corrigidos pelo efeito do filtro interno. Considerando a primeira derivada da varredura síncrona, os dados foram extraídos a 316,8 nm (Mudança de Stokes) e 352,0 nm (Mudança de Stokes= 58 nm) para os óleos essenciais de laranja doce e lavanda, respectivamente, com coeficientes de determinação acima de 0,99. Limites de quantificação de 8,0 microgamas mL-1 e 65,8 microgramas mL-1 foram obtidos, indicando que 0,46 porcento de óleo essencial de laranja doce e 3,69 porcento de óleo essencial de lavanda podem ser quantificados em misturas dos dois óleos. Misturas simuladas (proporções de volume de 25:75 porcento, 50:50 porcento e 75:25 porcento) também foram avaliadas com recuperações de 71,5 porcento a 128,9 porcento e coeficiente de variação entre 3,1 porcento e 11,6 porcento. Além disso, o método foi avaliado quanto ao seu impacto ecológico por meio de três métricas verdes (Analytical Eco-Scale, GAPI e AGREE) com resultados concordantes. / [en] A simple green analytical method for the quantification of sweet orange and lavender essential oils (EOs) content in blends was developed using synchronous fluorescence first derivative spectra and sample preparation by surfactant-free microemulsions (SFMEs). Excitation and emission wavelengths pairs (Absorbance measurements in the excitation wavelength/Absorbance measurements in the emission wavelength) were determined for both EOs (at 336/436 nm for sweet orange and at 330/388 nm for lavender). Optimization was conducted to establish the condition to prepare the SFMEs systems: 50 microlitres of oily phase containing EO diluted in octan-1-ol (1:4, v/v), 2.0 mL of water and propan-1-ol up to 5.0 mL final volume. Different proportions of EO in the oily phase were prepared for analytical curves construction to monitor curve s sensibility. Synchronous fluorescence measurements were performed, and the acquired data were corrected by inner filter effect. Considering the first derivative of the synchronous scanning, data were extracted at 316.8 nm (Stokes shift = 100 nm) and 352.0 nm (Stokes shift = 58 nm) for sweet orange and lavender EOs, respectively, with determination coefficients above 0.99. Limits of quantification of 8.0 micrograms mL-1 and 65.8 micrograms mL-1 were obtained indicating that 0.46 percent of sweet orange and 3.69 percent of lavender EOs can be quantified in mixtures. Simulated blends (25:75 percent, 50:50 percent and 75:25 percent, volume proportions) were also evaluated with recoveries of 71.5 – 128.9 percent and coefficient of variation between 3.1 percent – 11.6 percent. Additionally, the method s greenness was evaluated through three green metrics (Analytical Eco-Scale, GAPI, and AGREE) with aligned results.