Academic literature on the topic 'HRMS Orbitrap'

Bruguiera cylindrica parts are commonly used in Chinese and Indian traditional medicine to treat diarrhea, fever, and many ailments. The present study aims non targeted analysis of key secondary metabolites of B. cylindrica by gas chromatography mass spectrometry (GC-MS) and ultra-high performance liquid chromatography hybrid quadrupole-Exactive-Orbitrap high resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap HRMS). GC-MS and UHPLC-Q-Exactive Orbitrap HRMS were utilized for metabolic profiling of ethyl acetate extract of B. cylindrica leaves. Key metabolites in the extract were identified and predicted based on chemical similarity using online databases such as ChemSpider and mzCloud. Thirty-six compounds belonging to different classes of secondary metabolites viz. flavonoids, fatty acids, fatty acid amides, carboxylic acids, and alkaloids were identified in the extract. Pentacyclic triterpenes like betulin, ursolic acid and a tropine, an alkaloid with potential pharmacological and therapeutic activities such as anticancer properties, neuromuscular blockers and antioxidants, were also identified. This study combined GC-MS and UHPLC-Q-Exactive Orbitrap HRMS with available online database for effective and rapid identification of bioactive metabolites in the ethyl acetate extract of mangrove without individual standard application. This is the first report on the HRMS based secondary metabolic profiling of B. cylindrica, with comprehensive map of its biologically important metabolites.

A targeted/non-targeted LC-HRMS/MS method for equine doping screening analysis was developed using a QE-Plus Orbitrap mass spectrometer combined with an in-house built compound database and spectral library.

The lack of effective screening strategies for high-grade serous carcinoma (HGSC), a subtype of ovarian cancer (OC) responsible for 70–80% of OC related deaths, emphasizes the need for new diagnostic markers and a better understanding of disease pathogenesis. Capillary electrophoresis (CE) coupled with high-resolution mass spectrometry (HRMS) offers high selectivity and sensitivity for ionic compounds, thereby enhancing biomarker discovery. Recent advances in CE-MS include small, chip-based CE systems coupled with nanoelectrospray ionization (nanoESI) to provide rapid, high-resolution analysis of biological specimens. Here, we describe the development of a targeted microchip (µ) CE-HRMS method, with an acquisition time of only 3 min and sample injection volume of 4nL, to analyze 40 target metabolites in serum samples from a triple-mutant (TKO) mouse model of HGSC. Extracted ion electropherograms showed sharp, baseline resolved peak shapes, even for structural isomers such as leucine and isoleucine. All calibration curves of the analytes maintained good linearity with an average R2 of 0.994, while detection limits were in the nM range. Thirty metabolites were detected in mouse serum with recoveries ranging from 78 to 120%, indicating minimal ionization suppression and good accuracy. We applied the µCE-HRMS method to biweekly-collected serum samples from TKO and TKO control mice. A time-resolved analysis revealed characteristic temporal trends for amino acids, nucleosides, and amino acid derivatives. These metabolic alterations are indicative of altered nucleotide biosynthesis and amino acid metabolism in HGSC development and progression. A comparison of the µCE-HRMS dataset with non-targeted ultra-high performance liquid chromatography (UHPLC)–MS results showed identical temporal trends for the five metabolites detected with both platforms, indicating the µCE-HRMS method performed satisfactorily in terms of capturing metabolic reprogramming due to HGSC progression while reducing the total data collection time three-fold.

Ranunculus sceleratus L.(RS) has shown various pharmacological effects in traditional Chinese medicine. In our previous study, the positive therapeutic effect on α-naphthylisothiocyanate induced intrahepatic cholestasis in rats was obtained using TianJiu treatment with fresh RS. However, the chemical profile of RS has not been clearly clarified, which impedes the research progress on the therapeutic effect of RS. Herein, an ultra-high performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) method was developed to rapidly separate and identify multiple constituents in the 80% methanol extract of RS. A total of sixty-nine compounds (19 flavonoids, 22 organic acids, 6 coumarins, 4 lignans, 14 nitrogenous compounds, and 4 anthraquinones) were successfully characterized. A total of 12 of these compounds were unambiguously identified by standard samples. Their mass spectrometric fragmentation pathways were investigated. It is worth noting that flavonoids and lignans were identified for the first time in RS. In this study, we successfully provide the first comprehensive report on identifying major chemical constituents in RS by UHPLC-Q-Orbitrap HRMS. The obtained results enrich the RS chemical profile, paving the way for further phytochemical study, quality control, and pharmacological investigation of RS.

Organophosphorus flame retardants (OPFRs) have been widely used in polymeric materials owing to their flame retardant and plasticizing effects. Investigating the fragmentation pathway of OPFRs is of great necessity for further discovering and identifying novel pollutants using orbitrap-based high-resolution mass spectrometry (HRMS). A total of 25 OPFRs, including alkyl, halogenated, and aromatic types, were analyzed in this study. The fragmentation pathways of the OPFRs were investigated using orbitrap-based HRMS with high-energy collision dissociation (HCD) in positive mode. The major fragmentation pathways for the three types of OPFRs are greatly affected by the substituents. In detail, the alkyl and halogenated OPFRs underwent three McLafferty hydrogen rearrangements, wherein the substituents were gradually cleaved to form the structurally stable [H4PO4]+ (m/z = 98.9845) ions. In contrast, the aromatic OPFRs would cleave not only the C-O bond but also the P-O bond, depending on the substituents, to form fragment ions such as [C6H7O]+ (m/z = 95.0495) or [C7H7]+ (m/z = 91.0530), among others. Using HRMS improved the accuracy of fragment ion identification, and the pathway became more evident. These fragmentation laws can provide identification information in pollutant screening work and theoretical references for the structural characterization of compounds with diverse substituent structures.

This study aimed to develop and validate a liquid chromatography/electrospray ionization-linear ion trap quadrupole-Orbitrap-high-resolution mass spectrometry (HPLC/ESI-LTQ-Orbitrap-HRMS) method to identify and quantify urinary microbial phenolic metabolites (MPM), as well as to explore the relationship between MPM and dietary (poly)phenols in Spanish adolescents. A total of 601 spot urine samples of adolescents aged 12.02 ± 0.41 years were analyzed. The quantitative method was validated for linearity, limit of detection, limit of quantification, recovery, intra- and inter-day accuracy and precision, as well as postpreparative stability according to the criteria established by the Association of Official Agricultural Chemists International. A total of 17 aglycones and 37 phase II MPM were identified and quantified in 601 spot urine samples. Phenolic acids were the most abundant urinary MPM, whereas stilbenes, hydroxytyrosol, and enterodiol were the least abundant. Urinary hydroxycoumarin acids (urolithins) were positively correlated with flavonoid and total (poly)phenol intake. An HPLC-ESI-LTQ-Orbitrap-HRMS method was developed and fully validated to quantify MPM. The new method was performed accurately and is suitable for MPM quantification in large epidemiological studies. Urinary lignans and urolithins are proposed as potential biomarkers of grain and nut intake in an adolescent population.

Tandem mass spectral databases are indispensable for fast and reliable compound identification in nontargeted analysis with liquid chromatography–high resolution tandem mass spectrometry (LC-HRMS/MS), which is applied to a wide range of scientific fields. While many articles now review and compare spectral libraries, in this manuscript we investigate two high-quality and specialized collections from our respective institutes, recorded on different instruments (quadrupole time-of-flight or QqTOF vs. Orbitrap). The optimal range of collision energies for spectral comparison was evaluated using 233 overlapping compounds between the two libraries, revealing that spectra in the range of CE 20–50 eV on the QqTOF and 30–60 nominal collision energy units on the Orbitrap provided optimal matching results for these libraries. Applications to complex samples from the respective institutes revealed that the libraries, combined with a simple data mining approach to retrieve all spectra with precursor and fragment information, could confirm many validated target identifications and yield several new Level 2a (spectral match) identifications. While the results presented are not surprising in many ways, this article adds new results to the debate on the comparability of Orbitrap and QqTOF data and the application of spectral libraries to yield rapid and high-confidence tentative identifications in complex human and environmental samples.

Sonchus arvensis, known as sowthistle, belongs to Asteraceae and contains numerous phenolic acids and flavonoids that exhibit antioxidants. The type of extraction solvent will affect biological activity level, resulting in different metabolite profiles that metabolomics approaches can evaluate by fingerprint analysis using FTIR spectrophotometry and UHPLC-Q-Orbitrap HRMS. Furthermore, the FTIR spectra and the metabolite profile of UHPLC-Q-Orbitrap HRMS were grouped using principal component analysis (PCA). This study aimed to clustering S. arvensis extracts based on different extracting solvents using the FTIR spectra and the detected metabolites and evaluate the free radical scavenging activity. The 50% ethanol extract gave higher free radical scavenging activity and more metabolites than the ethanol p.a. and water extracts. It indicates that the free radical scavenging activity is affected by the metabolites contained in the extract. Using a combination of the FTIR spectra and the peak area of the identified metabolites, S. arvensis extract can be grouped according to the extracting solvent. Thus, the extracting solvent affects the composition of the metabolites, resulting in different free radical scavenging activity levels.

Objective: To compare the effect of fermentation on the chemical constituents of Gastrodia Tuder Halimasch Powder (GTHP), to establish its fingerprinting and multicomponent content determination, and to provide a basis for the processing, handling, and clinical application of this herb. Methods: Ultra-high-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was used to conduct a preliminary analysis of the chemical constituents in GTHP before and after fermentation. High-performance liquid chromatography (HPLC) was used to determine some major differential components of GTHP and establish fingerprints. Cluster analysis (CA), and principal component analysis (PCA) were employed for comprehensive evaluation. Results: Seventy-nine compounds were identified, including flavonoids, organic acids, nucleosides, terpenoids, and others. The CA and PCA results showed that ten samples were divided into three groups. Through standard control and HPLC analysis, 10 compounds were identified from 22 peaks, namely uracil, guanosine, adenosine, 5-hydroxymethylfurfural (5-HMF), daidzin, genistin, glycitein, daidzein, genistein, and ergosterol. After fermentation, GTHP exhibited significantly higher contents of uracil, guanosine, adenosine, 5-hydroxymethylfurfural, and ergosterol and significantly lower genistein and daidzein contents. Conclusions: The UHPLC-Q-Orbitrap HRMS and HPLC methods can effectively identify a variety of chemical components before and after the fermentation of GTHP. This study provides a valuable reference for further research on the rational clinical application and quality control improvement of GTHP.

The increasing number of foodomics studies based on non-targeted methods shows that this approach is considered by scientists to be an efficient way of evaluating food safety and quality. In the last few years, high resolution mass spectrometry (HRMS) has indeed gained wider acceptance thanks to the high selectivity and sensitivity achievable during analysis. In contrast to the classic unit-mass-resolution MS/MS approach, HRMS provides more information on sample composition through collection of full-scan spectra and thanks to the possibility of performing retrospective data analysis. Consequently, even without defining compound-specific tuning, HRMS data can be used for identification of suspect compounds or for structural elucidation of unknowns. HRMS can only compete with classic MS/MS methods using the targeted approach, even if it allows the simultaneous detection of a higher number of compounds. In contrast, HRMS is a more promising approach when suspect and non-targeted screening analysis is performed, not only because full-scan and retrospective analysis is feasible, but also because the accurate mass of both precursor and product ions and their isotope patterns are provided. Furthermore, a non-targeted approach leads to specific profiling of biological systems through a wide selection of chemical descriptors, and provides the fingerprint of the system under investigation, useful for more easily identifying potential adulteration. The aim of this work was to extend comprehension of the three different HRMS approaches (nontargeted, suspect and targeted screening), examining both their potential and limitations in relation to the analysis of the compounds of interest in different matrices. Initially, the objectives concerned the possibility of developing new methods – one for each HRMS screening approach – for the analysis of glycosides and phenolic compounds, in order to furnish innovative and well-performing analytical tools for food safety and quality control at all stages of food production, processing and distribution. Furthermore, they regarded the possibility of investigating the nature and occurrence of glycosides and phenolic compounds in widely consumed beverage and food commodities, such as grape, wine, spirits, cocoa and honeys. The thesis, which includes both published and in litteris papers, describes newly developed analytical methods and their technological applications in the study of different matrices, focusing on: - Investigation of Neutral Loss experiments as an instrument for non-targeted screening analysis of glycosides, and performance evaluation of this analytical approach in relation to the glycosidic profiling of international monovarietal wines; - Investigation of the distribution of free and glycosylated low-molecular-weight phenolic compounds in skin and seeds of color-rich Vitis vinifera grapes cultivated in southern Uruguay, combining Neutral loss experiment and suspect screening analysis; - Investigation of the selectivity and sensitivity of the HRMS approach for targeted analysis of free and glycosylated low-molecular-weight phenolic compounds and suspect screening analysis of the latter, together with evaluation of the best sample clean-up procedure for reducing matrix interference; - Investigation of the distribution of free and glycosylated low-molecular-weight phenolic compounds in skin, pulp and seeds, focusing on both Vitis vinifera and hybrid grapes; - Investigation of the impact of alcoholic fermentation on the free and glycosylated phenolic profile of wines produced from grapes of hybrid varieties; - Study of the occurrence of glycosylated low-molecular-weight phenolic compounds in tannins of different botanical origin, in order to evaluate the alteration of the phenolic profile of wines after tannin addition; - Study of the free phenolic composition of wood barrels, in order to evaluate phenolic enrichment during ageing, and investigation of the possible impact of different barrel sanitation treatments on the phenolic transfer from wood to wine; - Study of the free and glycosylated low-molecular-weight phenolic profile in Primitivo di Manduria and Negroamaro wines of different vintages and evaluation of the effect of wine ageing; - Investigation of the possibility of considering free or glycosylated low-molecular-weight phenolic compounds as new markers for beverages and food characterization and their geographical traceability, focusing on wine, spirits, vinegar, food tannins, cocoa beans and honeys; - Implementation of investigative methods of suspect screening analysis using naturally rich matrices as available sources of compounds of interest. This approach was applied on plant products for alkaloid identification; - Investigation of the selectivity and sensitivity of the HRMS approach for suspect screening analysis of flavonoids in flowering plant (C. pareira) extracts.

Bien que représentant une petite proportion de la matière organique (MO) des sols, la MO dissoute (MOD) est au cœur de nombreux processus biogéochimiques dans l’environnement. Sa composition reflète ses sources de production, et des processus auxquels elle a été exposée. Cependant, les processus ayant lieu dans les premiers instants suivant la production de MOD naturelle sont encore mal connus, du fait de la haute réactivité de celle-ci. Dans les environnements terrestres, la litière est une des sources initiales majeures de MOD, avant d’être dégradée. Les travaux effectués au cours de ce doctorat se sont donc focalisés sur la caractérisation des MOD produites par différentes espèces végétales, ainsi que sur leurs évolutions qualitatives et quantitatives, au cours de la biodégradation. Le lien entre la composition de la couverture végétale et la signature moléculaire de la MOD a également été évalué, afin de déterminer l’influence de la végétation sur les propriétés des MOD naturelles. Les MO extractibles à l’eau (WEOM) produites par 6 espèces végétales (C. stellaris, F. nivalis, E. vaginatum, B. nana, B. pubescens, et Salix sp.) ont été caractérisées grâce à l’utilisation de techniques analytiques complémentaires. Les résultats ont montré que la quantité et la composition de la WEOM produite par les végétaux étaient dépendantes du type fonctionnel de plante (PFT). Il a également été mis en avant que certains proxys classiquement utilisés pour caractériser la MOD n’étaient pas applicables à l’étude de WEOM non transformées. Néanmoins, la confrontation des proxys appropriés a permis d’affirmer que les graminées étaient potentiellement moins biodégradables que les lichens, mais plus que les arbustes. Des expériences de biodégradation de WEOM ont ensuite été effectuées en conditions contrôlées. Pour cela, 4 espèces appartenant à différents PFT ont été sélectionnées, et leurs WEOM extraites. Ces espèces sont C. stellaris (lichen), E. vaginatum (carex), A. polifolia (arbuste persistant), et B. nana (arbuste à feuilles caduques). Les résultats montrent une consommation significativement plus importante des WEOM produites par C. stellaris et E. vaginatum, que A. polifolia et B. nana en fin d’incubation. En parallèle, l’accumulation des composés récalcitrants dans les WEOM a été observée, en particulier pour B. nana. Ces résultats reflètent des biodégradabilités plus importantes pour les WEOM de lichens et graminées que pour celles des arbustes. La diversité moléculaire de la WEOM a également significativement diminué pour C. stellaris et E. vaginatum, et à l’inverse, a augmenté pour B. nana. Des processus de biodégradation propres aux espèces produisant ces WEOM ont donc été mise en évidence. Enfin, des échantillons de MOD ont été prélevés dans des écosystèmes Arctiques aux compositions de couvertures végétales contrastées. Ces MOD ont été analysées par spectrométrie de masse à haute résolution (HRMS). Leurs signatures moléculaires ont été confrontées les unes aux autres, puis comparées à celles des WEOM issues des végétaux. Une majorité de composés sont communs à toutes les MOD. Malgré ces composés ubiquistes, les écosystèmes peuvent être distingués à partir des compositions moléculaires de leurs MOD. Pour chaque espèce végétale étudiée, la contribution de celle-ci à la couverture totale (en % de surface) a été confrontée à la contribution des molécules spécifiques à cette espèce à la composition totale de la MOD. Ces comparaisons ont montré une corrélation positive significative pour B. nana, contrairement aux autres espèces étudiées. L’ensemble des résultats de cette thèse montrent que les quantités et les qualités de WEOM produites par les végétaux sont spécifiques, et par conséquence, leurs biodégradabilités aussi. Ainsi, les MOD produites par les différentes espèces végétales n’auront pas les mêmes dynamiques dans l’environnement. Lors de leur biodégradation, les MOD issues des végétaux sont homogénéisées
Although dissolved organic matter (DOM) represents a small fraction of soil organic matter (OM), it is involved in many biogeochemical processes in the environment. Its composition reflects its sources of production, and the processes it has been exposed to. However, the processes taking place immediately after DOM production are still poorly understood, due to its high reactivity. In terrestrial environments, fresh leaf litter is one of the major initial sources of DOM, before it is degraded. This PhD focused on the characterisation of DOM produced by different vegetation species, and the evolution of their properties during biodegradation. The relationship between the composition of vegetation cover and the molecular signature of DOM has been assessed, in order to determine the influence of vegetation on DOM properties in the environment. The water extractable OM (WEOM) produced by 6 vegetation species (C. stellaris, F. nivalis, E. vaginatum, B. nana, B. pubescens, and Salix sp.) were characterised through complementary analytical technics. The results showed that the quantity and composition of WEOM produced by vegetation were different between plant functional types (PFT). It was also pointed out that some proxies commonly used to characterise DOM were not relevant to the study of unprocessed WEOM. However, the comparison of relevant proxies indicated that graminoids were potentially less biodegradable than lichens, but more than shrubs. WEOM biodegradation experiments were carried out under controlled conditions. For this purpose, 4 species belonging to different PFT were selected, and their WEOM extracted. These species were C. stellaris (lichen), E. vaginatum (sedge), A. polifolia (dwarf evergreen shrub), and B. nana (deciduous dwarf shrub). The results showed a significantly higher consumption of WEOM produced by C. stellaris and E. vaginatum, than A. polifolia and B. nana, at the end of the experiment. In the meantime, the accumulation of recalcitrant compounds in WEOM was observed, especially for B. nana. These results put into light a more important biodegradability of lichens and graminoids compared to shrubs. Furthermore, the molecular diversity of WEOM significantly decreased for C. stellaris and E. vaginatum, whereas it increased for B. nana. Species-specific biodegradation processes have been brought to light. Finally, samples of DOM were collected from Arctic ecosystems with contrasted vegetation cover compositions. DOM samples were analysed by high resolution mass spectrometry (HRMS). Their molecular signatures were compared to each other, and to WEOM produced by vegetation. A great amount of compounds were common to all DOM samples. Despite these ubiquitous compounds, it was possible to discriminate ecosystems, based on the molecular compositions of their DOM. The contributions of each species to the vegetation cover were compared to the contributions of their WEOM to the molecular signature of DOM. These comparisons showed a significant positive correlation for B. nana, but not for other studied species. The results of this thesis show that the quantity and composition of produced WEOM are vegetation-specific. Consequently, WEOM biodegradability is also vegetation-specific. Therefore, the DOM produced by different vegetation species won’t have the same dynamic in the environment. Furthermore, the WEOM produced by vegetation are homogenised during their biodegradation

La pollution des eaux est une problématique majeure qui affecte tant les écosystèmes aquatiques que sur la santé humaine. Par conséquent, la prévention et la surveillance des pollutions constituent donc un enjeu prioritaire afin d’éviter la dissémination de ces polluants. Dans ce contexte, il est essentiel de recourir à la miniaturisation des systèmes et à des méthodes analytiques afin de surveiller en temps réel l'évolution de la pollution sur le terrain. Dans le cadre de ces travaux de thèse, tout d’abord, la préparation et l’évaluation de µ-colonnes de types multicanaux en GC a été réalisée. Des dépôts avec différentes phases stationnaires ont été effectués et des tests en GC unidimensionnel puis un système bidimensionnel « GC×µGC » avec un modulateur microfluidique ont été réalisés avec succès. Par la suite, une méthode d’extraction par sorption sur barreau magnétique (SBSE) suivi d’une thermo-désorption (TD) et d’une analyse non ciblée par spectrométrie de masse à haute résolution (HRMS) a été développée. Afin de pallier les contraintes de la SBSE classique, de nouvelles phases ont été déposées sur les barreaux magnétiques visant ainsi à améliorer les rendements d’extraction des composés les plus polaires. Enfin, des extractions SBSE des polluants ont été effectuées sur des eaux naturelles provenant d’Algérie et de France suivies d’analyses non ciblées par TD-GC-HRMS OrbitrapTM. Des informations sur la qualité des eaux de surfaces en Algérie mais aussi en France quant au niveau de leur contamination ont pu être données et les différents polluants identifiés ont été ensuite classés selon des niveaux confiances basés sur une échelle d’identification récentes
Water pollution is a major problem that affects both aquatic ecosystems and human health. Therefore, the prevention and the control of the dissemination of contaminants in the environment has become a priority. To achieve that, the use of miniaturized analytical systems to control pollution in real-time on-site appears necessary. The evaluation of µ-columns with radially elongated pillars was performed using different stationary phases. Then the performances of the prepared µ-columns were evaluated on conventional GC and in a comprehensive two-dimensional system « GC×µGC » with a microfluidic modulator as a second columns. Afterwards, a stir bar sportive extraction (SBSE) method and a non-targeted analysis one using GC coupled to a high-resolution mass spectrometry (HRMS) were developed. In order to overcome the limitations of SBSE and improve the extraction yields, new SBSE phases were used for the coating of the stir bar. Finally, SBSE extractions of contaminants were performed on naturel waters collected from Algeria and France followed by a non-target analysis using TD-GC-HRMS OrbitrapTM. Information on the quality of surface waters and the level of pollution were collected for both countries and the annotation of the identified compounds were then classified according to levels of confidence

Les plantes médicinales constituent une source inexhaustible de composés (des produits naturels - PN) utilisé en médecine pour la prévention et le traitement de diverses maladies. L'introduction de nouvelles technologies et méthodes dans le domaine de la chimie des produits naturels a permis le développement de méthodes ‘high throughput’ pour la détermination de la composition chimique des extraits de plantes, l'évaluation de leurs propriétés et l'exploration de leur potentiel en tant que candidats médicaments. Dernièrement, la métabolomique, une approche intégrée incorporant les avantages des technologies d'analyse moderne et la puissance de la bioinformatique s’est révélé un outil efficace dans la biologie des systèmes. En particulier, l'application de la métabolomique pour la découverte de nouveaux composés bioactifs constitue un domaine émergent dans la chimie des produits naturels. Dans ce contexte, le genre Acronychia de la famille des Rutaceae a été choisi sur la base de son usage en médecine traditionnelle pour ses propriétés antimicrobienne, antipyrétique, antispasmodique et anti-inflammatoire. Nombre de méthodes chromatographiques modernes, spectrométriques et spectroscopiques sont utilisées pour l'exploration de leur contenu en métabolites suivant trois axes principaux constituant les trois chapitres de cette thèse. En bref, le premier chapitre décrit l’étude phytochimique d’Acronychia pedunculata, l’identification des métabolites secondaires contenus dans cette espèce et l'évaluation de leurs propriétés biologiques. Le deuxième chapitre vise au développement de méthodes analytiques pour l'identification des dimères d’acétophénones (marqueurs chimiotaxonomiques du genre) et aux stratégies utilisées pour la déréplication de ces différents extraits et la caractérisation chimique des composés par UHPLC-HRMSn. Le troisième chapitre se concentre sur l'application de méthodologies métabolomique (RMN et LC-MS) pour l'analyse comparative (entre les différentes espèces, origines, organes), pour des études chimiotaxonomiques (entre les espèces) et pour la corrélation des composés contenus avec une activité pharmacologique
Medicinal plants constitute an unfailing source of compounds (natural products – NPs) utilised in medicine for the prevention and treatment of various deceases. The introduction of new technologies and methods in the field of natural products chemistry enabled the development of high throughput methodologies for the chemical composition determination of plant extracts, evaluation of their properties and the exploration of their potentials as drug candidates. Lately, metabolomics, an integrated approach incorporating the advantages of modern analytical technologies and the power of bioinformatics has been proven an efficient tool in systems biology. In particular, the application of metabolomics for the discovery of new bioactive compounds constitutes an emerging field in natural products chemistry. In this context, Acronychia genus of Rutaceae family was selected based on its well-known traditional use as antimicrobial, antipyretic, antispasmodic and anti-inflammatory therapeutic agent. Modern chromatographic, spectrometric and spectroscopic methods were utilised for the exploration of their metabolite content following three basic axes constituting the three chapters of this thesis. Briefly, the first chapter describes the phytochemical investigation of Acronychia pedunculata, the identification of secondary metabolites contained in this species and evaluation of their biological properties. The second chapter refers to the development of analytical methods for the identification of acetophenones (chemotaxonomic markers of the genus) and to the dereplication strategies for the chemical characterisation of extracts by UHPLC-HRMSn. The third chapter focuses on the application of metabolomic methodologies (LC-MS & NMR) for comparative analysis (between different species, origins, organs), chemotaxonomic studies (between species) and compound-activity correlations

AbstractFour different analytical methods were used for the determination of (1) polybrominated diphenyl ethers (PBDE), (2) hexabromocyclododecanes (HBCDD), (3) chlorinated paraffins (CP) and (4) polychlorinated naphthalenes (PCN) in human milk samples of the WHO/UNEP-coordinated exposure studies. As a laboratory accredited according to EN ISO/IEC 17025, a comprehensive quality control program was applied to assure the reliability of results. This included procedural blanks, the use of numerous quality control samples as in-house reference materials and the participation in proficiency tests (PTs). Trueness was estimated from the PT samples using the assigned values.The mean absolute deviation of the sum parameters ∑PBDE6 and ∑PBDE7 from the assigned values of 53 PT samples analysed between 2006 and 2021 was 12% and 14%, respectively.For α-HBCDD as the most abundant diastereomer and the sum of α-, β- and γ-HBCDD, deviations of the reported value from the assigned value of the proficiency tests (31 samples, analysed between 2007 and 2021) were in most cases below 40% over a large concentration range, e.g., for α-HBCDD, between 0.0084 and 19 ng/g fw. For concentrations above 0.5 ng/g lipid, the deviation was in the range of approximately 0–30%.For short-chain and medium-chain CP (SCCP and MCCP) all z-scores achieved in interlaboratory comparisons during 2017–2020 were within ±2 z and therefore satisfactory (13 PT samples were analysed for ΣCP, ΣSCCP and ΣMCCP using the GC-ECNI-Orbitrap-HRMS method, eight results achieved for ΣCP using the GC-EI-MS/MS method).Due to the lack of available proficiency tests for PCN at the time of measuring the human milk samples of the 2016–2019 period, an external validation for control of the trueness was performed through an interlaboratory comparison with an independent laboratory. The deviation of the ΣPCN13 in five test samples between the external laboratory and CVUA Freiburg was in the range from 3 to 20%. At a later stage (in 2021), the laboratory participated successfully in the first interlaboratory comparison study on PCN congeners in cod liver oil. The z-scores for seven congeners and two sum parameters were within ±2 z and therefore satisfactory. Also, the results for other of the altogether 26 PCN congeners were in accordance with the median values reported by all participants.As a result, the determination of PBDE, HBCDD, CP and PCN in human milk samples of the WHO/UNEP-coordinated exposure studies followed the strict rules of the accreditation system and the general criteria for the operation of testing laboratories as laid down in EN ISO/IEC 17025.

The most common mycotoxins are aflatoxins (AFs), which are produced by strains of various species of molds in the genus Aspergillus (A. flavus, A. parasiticus, A. nomius and A. tamarii) and can grow on many foods, mainly peanuts, maize and cottonseed. AFs are currently considered to be the most hazardous mycotoxins to health, in particular because of their hepatocellular carcinogenic potential. The main aflatoxins are B1 (AFB1), B2 (AFB2), G1 (AFG1) and G2 (AFG2) although many other derivatives have been described. In addition, animals consuming contaminated feeds are able to metabolize them by hydroxylation in a certain position, yield for example aflatoxin M1 (AFM1) and aflatoxin M2 (AFM2) from AFB1 and AFB2, respectively. Nowadays, only the four main AFs and one hydroxylated metabolite (AFM1) are routinely analyzed. High resolution mass spectrometry (HRMS) using Orbitrap or time-of-flight (TOF) mass analysers is a trend for AFs determination, allowing to determine AFs and their derivatives for which there are no commercial standards available, in order to carry out metabolization studies, exposure assessment or monitoring modified AFs in food. The aim of this study is to show the recent trends in analytical methods based on LC-HRMS for determination of AFs.

Recent high resolution experimental studies of the electronic spectra of triatomic dihydrides and their ions have provided a severe test of current models of electronic orbital angular momentum-nuclear - vibrational angular momentum coupling. This coupling is associated with the breakdown of the Born-Oppenheimer separation of electronic orbital and nuclear motion, the Renner-Teller effect, and also with spin-orbit coupling.

For many years, scientists have studied the spectroscopy of van der Waals complexes in past to understand intermolecular interactions and potential energy surfaces. There are abundant experiments and theoretical calculations on the closed-shell van der Waals complexes.1,2 Relatively speaking, the open-shell complexes have attracted much less attention until recently. The sparsity of information is due to both the difficulty of preparing the species and the complexity of their spectroscopy, which involves both unquenched electronic orbital and spin angular momenta. In the past four years, there have been several experimental and theoretical papers centered on Ar•OH/D and Ne•OH/D.3,4 However, except for one microwave experiment5 the previous works lack information about fine and hyperfine structure due to the resolution limit of dye laser used in the laser-induced fluorescence (LIF) studies.