Devenir environnemental des antidépresseurs dans les rejets urbains par chromatographie liquide à haute performance couplée à la spectrométrie de masse en tandem

Les troubles reliés à la dépression, l’épuisement professionnel et l’anxiété sont de plus en plus répandus dans notre société moderne. La consommation croissante d’antidépresseurs dans les différents pays du monde est responsable de la récente détection de résidus à l’état de traces dans les rejets urbains municipaux. Ainsi, ces substances dites « émergentes » qui possèdent une activité pharmacologique destinée à la régulation de certains neurotransmetteurs dans le cerveau suscitent maintenant de nombreuses inquiétudes de la part de la communauté scientifique. L’objectif principal de ce projet de doctorat a été de mieux comprendre le devenir de plusieurs classes d’antidépresseurs présents dans diverses matrices environnementales (i.e. eaux de surfaces, eaux usées, boues de traitement, tissus biologiques) en développant de nouvelles méthodes analytiques fiables capables de les détecter, quantifier et confirmer par chromatographie liquide à haute performance couplée à la spectrométrie de masse en tandem (LC-QqQMS, LC-QqToFMS). Une première étude complétée à la station d’épuration de la ville de Montréal a permis de confirmer la présence de six antidépresseurs et quatre métabolites N-desmethyl dans les affluents (2 - 330 ng L-1). Pour ce traitement primaire (physico-chimique), de faibles taux d’enlèvement (≤ 15%) ont été obtenus. Des concentrations d’antidépresseurs atteignant près de 100 ng L-1 ont également été détectées dans le fleuve St-Laurent à 0.5 km du point de rejet de la station d’épuration. Une seconde étude menée à la même station a permis l’extraction sélective d’antidépresseurs dans trois tissus (i.e. foie, cerveau et filet) de truites mouchetées juvéniles exposées à différentes concentrations d’effluent dilué traité et non-traité à l’ozone. Un certain potentiel de bioaccumulation dans les tissus (0.08-10 ng g-1) a été observé pour les spécimens exposés à l’effluent non-traité (20% v/v) avec distribution majoritaire dans le foie et le cerveau. Une intéressante corrélation a été établie entre les concentrations de trois antidépresseurs dans le cerveau et l’activité d’un biomarqueur d’exposition (i.e. pompe N/K ATPase impliquée dans la régulation de la sérotonine) mesurée à partir de synaptosomes de truites exposées aux effluents. Une investigation de l’efficacité de plusieurs stations d’épuration canadiennes opérant différents types de traitements a permis de constater que les traitements secondaires (biologiques) étaient plus performants que ceux primaires (physico-chimiques) pour enlever les antidépresseurs (taux moyen d’enlèvement : 30%). Les teneurs les plus élevées dans les boues traitées (biosolides) ont été obtenues avec le citalopram (1033 ng g-1), la venlafaxine (833 ng g-1) et l’amitriptyline (78 ng g-1). Des coefficients de sorption expérimentaux (Kd) calculés pour chacun des antidépresseurs ont permis d’estimer une grande sorption des composés sertraline, desméthylsertraline, paroxetine et fluoxetine sur les solides (log Kd > 4). Finalement, un excellent taux d’enlèvement moyen de 88% a été obtenu après ozonation (5 mg L-1) d’un effluent primaire. Toutefois, la caractérisation de nouveaux sous-produits N-oxyde (venlafaxine, desmethylvenlafaxine) par spectrométrie de masse à haute résolution (LC-QqToFMS) dans l’effluent traité à l’ozone a mis en lumière la possibilité de formation de multiples composés polaires de toxicité inconnue.Mood disorders such as depression, burn-out and anxiety have increased in our modern society. Increasing amounts of antidepressant prescriptions around the world are now suspected to be the main cause of the recent detection of traces of antidepressant residues within urban wastewaters. These so-called “emerging” substances that possess pharmacological activity towards neurotransmitter regulation in the brain have raised serious concerns from the scientific community. The initial goal of the study was to better understand the fate of various classes of antidepressants present in different environmental matrices (e.g. surface waters, wastewaters, treatment sludge, and biological tissues) by developing novel reliable analytical methods that can detect, quantify and confirm antidepressants using high performance liquid chromatography coupled to tandem-mass spectrometry (LC-QqQMS,LC- QqToFMS). A preliminary study completed at the Montreal sewage treatment plant (STP) confirmed the presence of six antidepressants and four N-desmethyl metabolites in raw sewage (2 – 330 ng L-1). For this primary treatment (physico-chemical), low removal rates (≤ 15%) were obtained. Concentrations of antidepressant close to 100 ng L-1 were also detected directly in the St. Lawrence River at 0.5 km of the effluent outfall. A second study conducted at the same STP allowed the selective extraction of antidepressants in three biological tissues (e.g. liver, brain, and filet) dissected from juvenile brook trouts previously exposed to diluted untreated and treated effluents with ozone. Bioaccumulation of antidepressants was readily observed in fish tissues (0.08-10 ng g-1) for the specimens exposed to untreated effluent (20% v/v), with major distribution in liver and brain. During experiments, a significant correlation was established between the concentrations of three antidepressant detected in brain tissues and the activity of a selected biomarker of exposition (e.g. an N/K ATPase pump involved in the serotonin regulation) measured within dissected synaptosomes from trout exposed to effluents. Investigation of estimated treatment removal efficiencies from various Canadian STPs operating different disinfection modes showed that secondary treatments (biological) were more efficient than primary (physico- chemical) to remove antidepressants (mean removal rates : 30%). The highest amounts detected in treated sludge (biosolids) were obtained respectively with citalopram (1033 ng g-1), venlafaxine (833 ng g-1), and amitriptyline (78 ng g-1). Experimental calculated sorption coefficients (Kd) of each antidepressant predicted fairly good sorption capacities for sertraline, desmethylsertraline, paroxetine, and fluoxetine to solid matters (log Kd > 4). Finally, an excellent mean removal rate of 88% was obtained after ozonation (5 mg L-1) of a primary effluent. However, the characterization of new N-oxide side-products (venlafaxine, desmethylvenlafaxine) in ozonized effluent by high-resolution mass spectrometry (LC-QqToFMS) highlighted the possibility of formation of multiple polar compounds with unknown toxicity

Sorption Capacities of a Lignin-Based Electrospun Nanofibrous Material for Pharmaceutical Residues Remediation in Water

The threat of pharmaceutical residues in natural waters is a pressing concern in both developed and underdeveloped countries. Originating mostly from municipal and farms effluents, pharmaceuticals, poorly eliminated by traditional wastewater treatments enter the environment through sewage treatment plants discharges. Their adsorption on ecological adsorptive materials such as lignin may represent an interesting remediation solution. The present study sets out the sorption capacities and properties of a newly developed lignin-based nanofibrous material for typical pharmaceutical residues (fluoxetine, venlafaxine, ibuprofen, and carbamazepine) found in surface waters. This green biomaterial showed, in addition to its high recovery yield, excellent reusability through desorption (more than 90% recovered). As an example, adsorption levels reached 78 mg/g for adsorption of fluoxetine compared to 5–10, 49 and 75–80 for unfunctionalized silica, zeolites and ion-exchange resins respectively. The innovative approach reported therein perfectly meets the concept of circular economy sought in modern societies

La parole pamphlétaire chez deux «partipristes» : Paul Chamberland et Pierre Vallières

Les textes des jeunes intellectuels de Parti pris, élaborés autour de l'agonistique et du polémique, théâtre de violence et de luttes entre classes et entre valeurs à l'intérieur du champ social, représentent un cas singulier de la parole pamphlétaire québécoise circonscrite au contexte des années 1960. La présente étude veut questionner la fortune critique des textes pamphlétaires de Parti pris au Québec en mettant au jour les stratégies d'ordre rhétorique et discursif qu'ils recèlent. La visée politique révolutionnaire mise de l'avant par la revue est certainement celle qui a réussi le mieux à regrouper ses membres autour de l'identité québécoise (politique, économique, littéraire, artistique et culturelle). Parmi eux, Paul Chamberland, dont les textes varient de l'éditorial à la poésie, et Pierre Vallières avec son essai autobiographique Nègres blancs d'Amérique, sont peut-être les plus représentatifs de leur époque et des enjeux autour desquels gravitait la génération Parti pris. En faisant appel aux théories sur la parole polémique, à la rhétorique et à la pragmatique, notre recherche vise à éclairer l'articulation de la pensée de Chamberland et de Vallières, de même que la valeur littéraire de leurs oeuvres, voire leurs particularités stylistiques. En plus de dégager un aperçu des principales problématiques abordées par les animateurs de Parti pris, ce mémoire interroge l'intentionnalité qui se profile derrière le discours qui circulait dans la revue et au sein de la génération qui s'en réclamait.The texts of the young intellectuals that appeared in Parti pris, written about the antagonistic and contentious theatre of violence and strife between classes and values in the social field, represent a singular case of Quebec’s pamphleteering circumscribed in the context of the 1960’s. This study wishes to question the critical faculties of the pamphleteers' texts in Quebec by uncovering the discursive and rhetorical strategies. The revolutionary political purpose put forward by the revue is certainly one of most successful in terms of consolidating its members around the Quebec identity (political, economic, literary, artistic and cultural). Amongst them, Paul Chamberland, whose texts ranged from editorials to poetry, and Pierre Vallières with his autobiographical essay Nègres blancs d’Amérique, are perhaps the most representative of their time and of the issues around which revolved the generation that Parti pris was representing. Drawing on theories of controversy, rhetoric and pragmatic speeches, our research aims to inform the reader of the articulation of Chamberland and Vallières’s thought, as well as the literary value of their work and their stylistic peculiarities. In addition to identifying an overview of the main issues addressed by the Parti pris’s leaders, this research questions the intentions that lie behind the discourse circulating in the revue and in the generation that was claiming it

Les analyses médico-légales de salives: expertise vis-à-vis l'analyse des drogues

When intercepting an individual on the road for driving under the influence of drugs (DUID), urine and blood are currently the main biological matrices used for screening. The intimate or invasive character of these biological specimens is undoubtedly a major disadvantage during the collection of specimens. Over the past decades, saliva has turned out to be an interesting alternative matrix. Thus, saliva is already used in several countries for screening prevalent drugs such as amphetamines, 3,4-methylenedioxy-methamphetamine (MDMA), cocaine, cannabis, opiates and benzodiazepines. Despite many benefits reported with saliva analyses, the establishment of a good correlation between salivary and plasmatic levels remains a challenge in interpreting toxicological results. Can saliva become an alternative to the usual biological matrices and/or a complement in cases of drug-impaired driving? A critical analysis with Bayesian treatments of data is addressed through this article in order to promote a reflection on this proposed drug screening methodology. © 2017 Canadian Society of Forensic Science

Challenges Related to Three Cases of Fatal Intoxication to Multiple Novel Synthetic Opioids

In the last two decades, a large increase in opioid overdose death rates has been recorded in North America. This phenomenon, related to the misuse of prescription opioids, has been dubbed an “opioids crisis”. Recent years have seen the entrance of novel synthetic opioids (NSO) on the market, compounding the fatal intoxications issue. This brings several challenges for forensic toxicology laboratories: an increased number of cases, a large number of novel structurally similar compounds to include in screening analytical methods, the low concentration of drugs in biological fluids, and the challenging interpretation in the absence of sufficient literature. Three cases of fatal intoxication highlighting those challenges are presented, complete with post-mortem concentrations in cardiac blood, femoral blood and urine. Toxicological screening and quantitative analyses were performed on the biological specimens. In the first and second cases, furanylfentanyl, U-47700 and 4-anilino-N-phenethylpiperidine (4-ANPP) were detected at similar concentrations in cardiac blood. In the third case, a total of seventeen different NSO were detected. All intoxications showed a combination of NSO and other drugs. These three cases appear to be the harbinger of an increased NSO prevalence in the province of Québec, Canada

Phytochemical Screening of Quaking Aspen (Populus tremuloides) Extracts by UPLC-QTOF-MS and Evaluation of their Antimicrobial Activity

The continual emergence of pathogen resistance is a recurring challenge and pushes for the development of antimicrobial compounds. Here, we investigated compounds from quaking aspen trees (Populus tremuloides) as potential antimicrobial agents. Several extractions using different solvents were realized, and corresponding antimicrobial activity was tested against eight microorganisms. Results revealed that polar extraction solvents including water, ethanol and methanol gave the best extraction yields (\u3e15.07%). Minimal inhibition concentration (MIC) and minimal bactericidal/fungicidal concentration (MBC/MFC) demonstrated that water extracts had the best antimicrobial activity by a weak to moderate inhibition of growth of all eight tested microorganisms in addition to having a bactericidal effect on three of them. The quaking aspen methanol extract also displayed antimicrobial activity but to a lower level than the water extract. Ultra-performance liquid chromatography quadrupole time-of flight mass spectrometry (UPLC-QTOF-MS) analysis led to the identification of 92 compounds, mainly polyphenols in both extracts, with 22 molecules previously known for their antimicrobial properties. According to the relative abundance, 4-hydroxybenzaldehyde (5.44% in methanol extract) and kaempferol (5.03% in water extract) were the most abundant antimicrobial compounds. Among antimicrobial molecules identified, nine were from the flavonoid family. The results of our study demonstrate the interest of using quaking aspen as source of antimicrobial compounds

Uptake, accumulation and metabolization of the antidepressant fluoxetine by Mytilus galloprovincialis

Fluoxetine, a selective serotonin re-uptake inhibitor (SSRI) antidepressant, is among the most prescribed pharmaceutical active substances worldwide. This study aimed to assess its accumulation and metabolization in the mussel Mytillus galloprovincialis, considered an excellent sentinel species for traditional and emerging pollutants. Mussels were collected from Ria Formosa Lagoon, Portugal, and exposed to a nominal concentration of fluoxetine (75 ng L-1) for 15 days. Approximately 1 g of whole mussel soft tissues was extracted with acetonitrile:formic acid, loaded into an Oasis MCX cartridge, and fluoxetine analysed by liquid chromatography with tandem mass spectrometry (LC-MSn). After 3 days of exposure, fluoxetine was accumulated in 70% of the samples, with a mean of 2.53 ng g(-1) dry weight (d.w.) and norfluoxetine was only detected in one sample (10%), at 3.06 ng g(-1) d.w. After 7 days of exposure, the accumulation of fluoxetine and norfluoxetine increased up to 80 and 50% respectively, and their mean accumulated levels in mussel tissues were up to 4.43 and 2.85 ng g(-1) d.w., respectively. By the end of the exposure period (15 days), both compounds were detected in 100% of the samples (mean of 9.31 and 11.65 ng g(-1) d.w., respectively). Statistical analysis revealed significant accumulation differences between the 3rd and 15th day of exposure for fluoxetine, and between the 3rd and 7th against the 15th day of exposure for norfluoxetine. These results suggest that the fluoxetine accumulated in mussel tissues is likely to be metabolised into norfluoxetine with the increase of the time of exposure, giving evidence that at these realistic environmental concentrations, toxic effects of fluoxetine in mussel tissues may occur. (C) 2016 Elsevier Ltd. All rights reserved