RESUME Le travail de thèse porte sur le développement d’électrodes sélectives originales et performantes pour l’analyse de composés d’intérêt pharmaceutique. La partie introductive traite des notions relatives à l’électrochimie mais également de notions sur les molécules médicamenteuses étudiées, en l’occurrence les principes antipaludéens et l’iode. La partie expérimentale se subdivise en deux parties distinctes selon le type d’électrodes sélectives auxquelles font appel les techniques électrochimiques. La première partie concerne l’élaboration, la caractérisation et l’application des électrodes potentiométriques à membrane polymérique incluant une paire d’ions et sélectives à diverses molécules organiques pharmacologiquement actives (antipaludéens). Leur application aussi bien en analyse pharmaceutique qu’en cinétique de dissolution est décrite. La deuxième partie est consacrée à l’élaboration d’un type de senseur ampérométrique original à pâte de carbone à base d’argent micronisé ou colloïdal et à la comparaison de ses performances avec l’électrode d’argent métallique. L’intérêt analytique est mis en évidence par la détermination quantitative des iodures. Les différents aspects susceptibles d’influencer leur comportement, dont la nature des agents précipitants (tétraphénylborate de sodium et le tétrakis (4-chlorophényl) borate de potassium) et de plastifiants ont été investigués. Les bonnes performances des ces électrodes en analyse quantitative ont permis d’explorer les possibilités de leur utilisation à l’étude de la cinétique de dissolution. L’ampérométrie à électrode à pâte de carbone modifiée à base d’argent à l’échelle micronisée (35% m/m) couplée à la chromatographie liquide ionique s’est avérée très sensible vis-à-vis des iodures en particulier et des halogénures en général. Les facteurs susceptibles d’influencer les grandeurs de séparation et la réponse de l’électrode ont été investigués et l’exploitation du signal ampérométrique permet le dosage sélectif et rapide de faibles concentrations en iodures. Les informations fournies par les mesures réalisées en voltampérométrie cyclique à l’aide des mêmes électrodes permettent une bonne compréhension mécanistique quant au mode de détection ampérométrique évitant ainsi toute confusion à ce sujet et permettant l’optimisation du processus de détection. ------------------------------------------------ ABSTRACT This thesis describes the development of original and high performance selective electrodes for the analysis of several pharmaceutical compounds. The introduction describes the pharmaceutical compounds of interest (antimalarial drugs and iodine) and provides an overall understanding of the electrochemical groundwork pertaining to their analysis. The experimental aspect of the thesis is divided into two parts, each according to the type of electrode and electrochemical technique used for the analysis. The first part describes the design, characterization, and application of polymer membrane based ion selective potentiometric electrodes. Selectivity was provided by including ion pairs of several antimalarial drugs into the membrane. The feasibility of use of these electrodes in pharmaceutical analysis as well as in dissolution trials is also described in this part. The second part describes the design of an original silver-modified carbon paste amperometric sensor and compares its performances to those of a plain metallic silver electrode. The electrode has been modified by silver microparticles or by silver nanoparticles. Quantitative iodine determination serves to prove the usefulness of this new sensor in analytical chemistry. Different aspects, such as the nature of the counter ions (sodium tetraphenylborate and potassium tetrakis (4-chlorophenyl) borate) and the plastifying agents that are likely to influence electrode behaviour have been investigated. Since the electrodes have been shown to perform well in quantitative analysis, the possibility of use in dissolution trials was explored. Micronized silver-modified carbon paste electrode (35% Ag m/m) coupled to anionic-exchange liquid chromatography with amperometric detection was shown to be very sensitive with regards to the assay of halogenides in general and iodide in particular. After having investigated the various factors likely to influence chromatographic separation and electrode response, it was shown that the sensor could be used to rapidly and selectively determine low iodide concentrations in complex samples. Cyclic voltammetric analysis provided information concerning the mechanisms allowing amperometric detection, thus allowing an optimisation of the detection procedures.

The chemistry and corrosion mechanisms associated with reduced sulfur compounds such as calcium sulfide, present in ground granulated blast-furnace slag (GGBFS), have been studied in high-density concrete, mortar and simulated pore-water environments. The high-density concrete and mortar samples were produced to replicate the high-density GGBFS concrete, in the dry storage containers (DSCs), used for radiation shielding from used nuclear fuel. Electrochemical measurements on embedded steel electrodes in high-density GGBFS concrete and mortar samples, showed that sulfide is capable of consuming oxygen to create a stable, reducing environment, though not in all cases, and the high-frequency electrolyte resistance increases with hydration time. Ion chromatography on simulated pore-water environments determined that thiosulfate is quite kinetically stable as a sulfide oxidation product and magnetite is capable of oxidizing sulfide. Microscopy has also been used to provide visual evidence of GGBFS hydration and elemental quantification of the hydrating microstructure in different environments.

The chemistry and corrosion mechanisms associated with reduced sulfur compounds such as calcium sulfide, present in ground granulated blast-furnace slag (GGBFS), have been studied in high-density concrete, mortar and simulated pore-water environments. The high-density concrete and mortar samples were produced to replicate the high-density GGBFS concrete, in the dry storage containers (DSCs), used for radiation shielding from used nuclear fuel. Electrochemical measurements on embedded steel electrodes in high-density GGBFS concrete and mortar samples, showed that sulfide is capable of consuming oxygen to create a stable, reducing environment, though not in all cases, and the high-frequency electrolyte resistance increases with hydration time. Ion chromatography on simulated pore-water environments determined that thiosulfate is quite kinetically stable as a sulfide oxidation product and magnetite is capable of oxidizing sulfide. Microscopy has also been used to provide visual evidence of GGBFS hydration and elemental quantification of the hydrating microstructure in different environments.

Per- and polyfluorinated substances (PFAS) are compounds that consist of a carbon chainbackbone that is partially or entirely fluorinated, with an addition of a functional group. SomePFAS are known as persistent organic pollutants (POPs) and have therefore been drawing a lot ofattention as well as increased concerns. PFAS have been detected in humans, wildlife and theenvironment and some have exhibited toxic effects such as hepatotoxicity, immunotoxicity,reproductive toxicity and endocrine disruption as well as being persistent and bioaccumulative.Serum, plasma and whole blood have been used as biomonitoring matrices in many studies toevaluate human exposure to PFAS. Restrictions have been applied to some PFAS, but thesecompounds are still ubiquitous. This study will investigate the performance (recovery, matrixeffect (ME) in terms of intra-/inter-day repeatability) of ion-pair extraction (IPE) and solid phaseextraction with weak anion exchange (SPE-WAX). The extraction methods were adapted fromliterature and 13 PFAS were selected for this work based on prior biomonitoring studies. Thetarget PFAS content was analyzed with liquid chromatography coupled with tandem massspectrometry (LC-MS/MS). The extraction methods were also compared for extractableorganofluorine (EOF) extraction in terms of blank levels as well as the amount extracted withdifferent methods; the EOF content was measured with combustion ion chromatography (CIC).The EOF levels were used to estimate the amount of unidentified organofluorine (UOF), to avoidunderestimating potential health hazards. Samples extracted using IPE had an average ionizationenhancement of 9%, while SPE-WAX showed an average ionization suppression of -1%. SPEWAXshowed higher average recoveries for procedural blanks (78%), horse serum (96%) andhuman serum (95%) in comparison to IPE (69%, 36%, 88%, respectively). The CIC analysis forEOF content was observed to be below MDL (<50 ng/mL F) with some contaminations observedin the procedural blanks.

Diploma thesis deals with the experimental study of transdermal transport of individual hydroxyacids and their combination with water-soluble vitamins. During this work the literature review was prepared, which was focused on the use of hydroxyacids in the cosmetic and pharmaceutical industries. At the same time the current state of use of water-soluble vitamins for topical applications was studied. Series of experiments was performed using Franz diffusion cells to simulate transdermal transport in vitro across cutaneous, synthetic and artificial Strat M ® membranes. The methodology of sample preparation and analysis of their transport properties was invented and optimized. The optimized methodology was subsequently used in a series of diffusion experiments in which the penetrated amount of hydroxyacids was analyzed by ion chromatography. The concentration of water-soluble vitamins was determined by HPLC. All examined active substances demonstrate positive penetration properties. The best results were obtained with combination of glycolic acid with pyridoxine.

The lithium-ion battery (LIB) recycling industry is currently under development to improve the yields for critical metals. However, the organic components of LIBs must also be handled, which may result in harmful chemical emissions as by-products. Of particular concern are highly persistent and mobile per- and polyfluoroalkyl substances (PFAS) that could be released during LIB recycling since some of these compounds have been linked with adverse health effects. In this work, an extensive literature review was conducted to determine the presence of fluorinated materials in state-of-the-art LIBs and the recycling conditions which could lead to the release of problematic PFAS. This information was used to develop a new analytical approach to capture the broadest range of organic and inorganic fluorine species in samples taken in different stages of the recycling process. This new method is based on a sequential extraction procedure using different solvents, followed by combustion ion chromatography (CIC) to quantify the potential emission of fluorine-containing chemicals of different polarities. The results show that organofluorine compounds are formed during recycling, particularly for the cathodes, indicating that PFAS might be present. For other samples, such as the NiMnCo salt product of recycling, only low fluorine levels were detected which implies almost complete removal. Future work should further outline the emission paths of these processes. This study highlights the necessity to further investigate the emissions related to fluorinated materials during LIB recycling and indicates that post-treatments or changes in conditions might be necessary to avoid the formation and emission of PFAS.

Under produktionen av kartong vid det integrerade massa- och kartongbruket, som ägs av Holmen Iggesund Paperboard AB, bildas klorat som är giftigt för vattenlevande organismer. Därför är det väsentligt att utsläppet av klorat till havet, via avloppsvattnet från bruket, hålls under de gränsvärden som fastställts. För att övervaka kloratutsläppet analyseras prover på avloppsvattnet rutinmässigt, och en jonkromatograf ämnades tas i drift för ändamålet. Jonkromatografi är en standardiserad metod för analys av klorat, som måste verifieras innan den tas i bruk. Inga explicita krav fanns på hur omfattande verifieringen skulle vara. Ett syfte med studien var därför att utveckla generella rekommendationer för omfattningen av verifieringen av en standardiserad analysmetod. Litteratur angående verifiering eftersöktes och summerades, och utifrån den togs en verifieringsplan för jonkromatografisk analys av klorat fram. Mätresultat som erhölls utvärderades statistiskt. Slutsatserna var; att verifiering bör planeras på ett sätt så att kalibrering och underhåll av instrumentet sker i samma omfattning som är tänkt vid rutinanvändning av analysmetoden; selektivitet bör testas tidigt, och riktiga prover bör analyseras i ett tidigt skede; omfattningen av verifieringen med avseende på provmatriser och koncentrationsnivåer ska återspegla de provmatriser och koncentrationer som analysmetoden kommer att innefatta i rutinarbetet; antalet försök som bör inkluderas beror på kraven som ställs på de olika egenskaper som definierar prestandan. Minst 6 försök på varje provmaterial var ett riktmärke för precision och riktighet, medan ett försök räckte vid utvärdering av selektivitet och instrumentets mätområde. För att kunna säkerställa god analyskvalité, är utbildning i analysmetodik en viktig del. Ytterligare ett syfte med denna studie var att undersöka utbildningsverksamhetens lärandemål, samt vilka utmaningar som fanns inom utbildningen i analysmetodik. Genom fokusgruppintervjuer och observationer samlades information inom utbildningsverksamheten och dess utmaningar. Utifrån det teoretiska ramverket självstyrd inlärning utfördes en deduktiv tematisk analys av den insamlade datan. Slutsatserna av arbetet löd: Det övergripande syftet med upplärningen inom en analysmetod var att personen som genomgått utbildningen ska kunna ansvara för att tillämpa analysmetoden självständigt utifrån instruktionen, ha kunskap om rimliga mätresultat, kunna reflektera över sitt arbete, samt ha kunskap om syftet med analysmetoden. Ingen standardiserad mall för vad som ska ingå i utbildningen inom en analysmetod fanns, vilket bidrog till osäkerheter angående huruvida likvärdig kompetens uppnåddes för personer under utbildning; dagens utbildningsupplägg inbjöd inte till att personen under upplärning tog på sig ansvaret för uppfyllandet av lärandemålen i den utsträckning som önskades. För att möjliggöra detta föreslogs att ett förberedande moment skulle införas, samt att den lärande skulle få mer tid och möjlighet att genomföra delar av utbildningen självständigt. / During the production of paperboard at the integrated pulp and paperboard mill, owned by Holmen Iggesund Paperboard AB, chlorate is formed, which is a toxic compound for aquatic organisms. It is therefore essential that the chlorate levels in the wastewater from the mill, which is released to the ocean, are below the established limit. In order to monitor the effluent of chlorate, wastewater samples are routinely analyzed, and for this purpose an ion chromatograph was intended to be put to use. Ion chromatography is a standardized method for chlorate analysis, which needs to be verified before being used for routine analyses. No explicit requirements regarding the extent of the verification existed. One purpose of this study was therefore to develop general recommendations regarding the extent of verification of a standardized analytical method. Literature regarding verification was sought for and summarized. Based on the literature, a plan for verifying ion chromatographic analysis of chlorate was constructed. The measurement results obtained were evaluated statistically. Conclusions drawn were: calibration and maintenance of the instrument during the verification process should reflect the frequency of maintenance and calibration planned during the routine use; selectivity should be tested early on, as well as real samples; the extent of the verification with respect to matrices and concentration levels should reflect those that will be included in the routine use of the analytical method; the number of experiments included depends on the requirements imposed on the performance characteristics of the method. At least 6 experiments for each sample was a good aim for verifying precision and trueness, while one experiment was enough for verification of selectivity and the working range of the instrument. In order to ensure satisfactory analysis quality, training in analytical methods is an important aspect. Another purpose of this study was to investigate the learning objectives of the educational activities as well as what challenges could be identified with respect to training in analytical methods. Through focus group interviews and observations, data was collected about the educational activities and challenges. Based on the theoretical framework self-directed learning, a deductive thematic analysis was performed. Conclusions were: The overall purpose of the training in analytical methods was that the person who underwent training should be able to independently apply the analytic method, with the aid of the analytical instruction, have the necessary knowledge about reasonable results, be able to reflect about their work and have knowledge about the purpose of the analytical method. No standardized template regarding what should be included in the training existed, which contributed to uncertainties regarding if equivalent knowledge was achieved for persons under training. The educational approach of today did not encourage the person under training enough to take responsibility for fulfilling the learning objectives. To enable this, it was suggested that a preparation element should be included in the training, and also that the person under training should get more time and opportunities to complete some of the training independently.

[pt] Este trabalho teve como objetivo caracterizar química e morfologicamente material particulado (PM2.5 e PM10) coletado na zona sul e oeste da cidade de Rio de Janeiro e na região metropolitana, utilizando técnicas como a Cromatografia de íons (CI), Espectrometria de Massas com Plasma Indutivamente Acoplado (ICPMS) e a Microscopia Eletrônica de Varredura acoplada ao Espectrômetro de RaiosX por Dispersão de Energia (MEV-EDX). Além disso, foram realizados ensaios toxicológicos com C. elegans para avaliar os efeitos da exposição ao material particulado (MP), nas diferentes frações de tamanho. Concentrações médias anuais de PM2.5 entre 7,40 +/- 3,96 (micrograma)m-3 e 17,4 +/- 7,38 (micrograma) m-3 foram medidas durante os anos 2015 e 2018, as quais foram inferiores ao padrão intermediário da qualidade do ar, estabelecido pelo CONAMA, registando-se as maiores médias anuais durante o 2016, ano em que foram realizados os Jogos Olímpicos. Resultados das análises químicas mostraram que o MP em todos os pontos de coleta estava constituído principalmente por espécies iônicas como Cl- , NO3 - , Na+ e SO4 2- e elementos como V, Ni, Cu, Cd, Sn e Pb, sendo determinadas apenas variações significativa (p menor que 0,05) nas concentrações de SO4 2- , NO3 - , Na+ , Cu e Sn, entre os períodos estudados. Através dos resultados das análises de MEV-EDX as partículas atmosféricas se classificaram segundo sua morfologia – Fuligem, esféricas, biológica e minerais- e segundo sua composição elementar – partículas com teor de enxofre, de cloro e de ferro -. Finalmente, efeitos tóxicos foram observados pela exposição ao PM10 e PM2.5 em organismos C. elegans, alterando parâmetros fisiológicos (e.g. crescimento e reprodução) e promovendo respostas dos mecanismos antioxidantes, como resultado do estresse oxidativo gerado por espécies presentes no MP. / [en] This work aimed to characterize chemically and morphologically particulate matter (PM2.5 and PM10) collected in the south and west zones of the city of Rio de Janeiro and in the metropolitan region, using techniques such as ion chromatography (IC), inductively coupled plasma mass spectrometry (ICP-MS) and Scanning electron microscopy- energy dispersive spectrometry (SEM-EDX). Annual mean concentrations of PM2.5 between 7,40 +/- 3,96 microgram m-3 e 17,4 +/- 7,38 microgram m-3 were measured during the years 2015 and 2018, which were lower than the intermediateair quality standard established by CONAMA, with the highest annual averages recorded during 2016, the year in which the Olympic Games were held. In addition, toxicological tests were performed with C. elegans to evaluate the effects of exposure to particulate matter (PM) in the different size fractions. Results of the chemical analysis showed that PM at all collection sites consists mainly of ionic species such Cl- , NO3 - , Na+ and SO4 2- and elements such as V, Ni, Cu, Cd, Sn and Pb, being determined only significant variations (p less than 0,05) in the concentrations of SO4 2- , NO3 - , Na+ , Cu, and Sn, between the studied periods. Based on the results of the SEM-EDX analysis, atmospheric particles were classified according to their morphology – Soot, spherical, biological and minerals- and according to their elemental composition – particles with sulfur, chlorine and iron content. Finally, toxic effects were observed by exposure C. elegans organisms to PM10 and PM2.5, altering physiological parameters (e.g growth and reproduction) and promoting antioxidant mechanisms responses, as a result of oxidative stress generated by compounds present in the PM.

RESUME<p><p>Le travail de thèse porte sur le développement d’électrodes sélectives originales et performantes pour l’analyse de composés d’intérêt pharmaceutique. <p><p> La partie introductive traite des notions relatives à l’électrochimie mais également de notions sur les molécules médicamenteuses étudiées, en l’occurrence les principes antipaludéens et l’iode.<p><p> La partie expérimentale se subdivise en deux parties distinctes selon le type d’électrodes sélectives auxquelles font appel les techniques électrochimiques.<p><p> La première partie concerne l’élaboration, la caractérisation et l’application des électrodes potentiométriques à membrane polymérique incluant une paire d’ions et sélectives à diverses molécules organiques pharmacologiquement actives (antipaludéens). Leur application aussi bien en analyse pharmaceutique qu’en cinétique de dissolution est décrite.<p><p> La deuxième partie est consacrée à l’élaboration d’un type de senseur ampérométrique original à pâte de carbone à base d’argent micronisé ou colloïdal et à la comparaison de ses performances avec l’électrode d’argent métallique. L’intérêt analytique est mis en évidence par la détermination quantitative des iodures.<p><p> Les différents aspects susceptibles d’influencer leur comportement, dont la nature des agents précipitants (tétraphénylborate de sodium et le tétrakis (4-chlorophényl) borate de potassium) et de plastifiants ont été investigués.<p>Les bonnes performances des ces électrodes en analyse quantitative ont permis d’explorer les possibilités de leur utilisation à l’étude de la cinétique de dissolution.<p><p> L’ampérométrie à électrode à pâte de carbone modifiée à base d’argent à l’échelle micronisée (35% m/m) couplée à la chromatographie liquide ionique s’est avérée très sensible vis-à-vis des iodures en particulier et des halogénures en général. Les facteurs susceptibles d’influencer les grandeurs de séparation et la réponse de l’électrode ont été investigués et l’exploitation du signal ampérométrique permet le dosage sélectif et rapide de faibles concentrations en iodures. Les informations fournies par les mesures réalisées en voltampérométrie cyclique à l’aide des mêmes électrodes permettent une bonne compréhension mécanistique quant au mode de détection ampérométrique évitant ainsi toute confusion à ce sujet et permettant l’optimisation du processus de détection.<p>------------------------------------------------<p>ABSTRACT<p><p>This thesis describes the development of original and high performance selective electrodes for the analysis of several pharmaceutical compounds. <p><p>The introduction describes the pharmaceutical compounds of interest (antimalarial drugs and iodine) and provides an overall understanding of the electrochemical groundwork pertaining to their analysis.<p><p>The experimental aspect of the thesis is divided into two parts, each according to the type of electrode and electrochemical technique used for the analysis.<p>The first part describes the design, characterization, and application of polymer membrane based ion selective potentiometric electrodes. Selectivity was provided by including ion pairs of several antimalarial drugs into the membrane. The feasibility of use of these electrodes in pharmaceutical analysis as well as in dissolution trials is also described in this part.<p><p>The second part describes the design of an original silver-modified carbon paste amperometric sensor and compares its performances to those of a plain metallic silver electrode. The electrode has been modified by silver microparticles or by silver nanoparticles. Quantitative iodine determination serves to prove the usefulness of this new sensor in analytical chemistry.<p><p>Different aspects, such as the nature of the counter ions (sodium tetraphenylborate and potassium tetrakis (4-chlorophenyl) borate) and the plastifying agents that are likely to influence electrode behaviour have been investigated. <p><p>Since the electrodes have been shown to perform well in quantitative analysis, the possibility of use in dissolution trials was explored.<p><p>Micronized silver-modified carbon paste electrode (35% Ag m/m) coupled to anionic-exchange liquid chromatography with amperometric detection was shown to be very sensitive with regards to the assay of halogenides in general and iodide in particular. After having investigated the various factors likely to influence chromatographic separation and electrode response, it was shown that the sensor could be used to rapidly and selectively determine low iodide concentrations in complex samples. Cyclic voltammetric analysis provided information concerning the mechanisms allowing amperometric detection, thus allowing an optimisation of the detection procedures.<p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished