Analysis, fate and toxicity of chiral non-steroidal anti-inflammatory drugs in wastewaters and the environment: a review.

Non-steroidal anti-inflammatory drugs (NSAIDs) are found in the aquatic environment globally. Such drugs including naproxen, ibuprofen and ketoprofen are chiral molecules. Enantiomers of those drugs have identical physicochemical properties but can behave and interact differently in chiral environments due to differences in their three-dimensional shape. This results in enantiospecific differences in environmental fate and toxicity, which is often overlooked. Therefore, we review the analytical methods, occurrence and fate, and toxicity of chiral non-steroidal anti-inflammatory drugs at the enantiomeric level. The advancement of enantioselective chromatography methods, particularly the use of polysaccharide-based stationary phases, has enabled trace determination of enantiomers in complex environmental matrices. Macrocosm and microcosm studies of engineered and natural environments revealed that such drugs can undergo both enantioselective degradation and chiral inversion. Enantioselectivity has been reported during wastewater treatment, in surface waters and in agricultural soils. The use of microcosms spiked with individual enantiomers over racemates is essential to evaluate these degradation and inversion fate processes. The chiral inversion process whereby one enantiomer converts into its antipode can be significant if the more toxic enantiomers are formed. Existing enantiospecific effect studies report less than an order of magnitude difference in enantiomer toxicity. However, toxicity data for enantiomers are limited and further research is needed to better appreciate the environmental risk at the enantiomeric level

Degradation of okadaic acid in seawater by UV/TiO2 photocatalysis: proof of concept.

The consumption of contaminated shellfish with marine toxins causes adverse socioeconomical, environmental and health impacts. The marine toxin okadaic acid (OA) provokes diarrhetic shellfish poisoning (DSP) syndrome characterized by severe gastrointestinal symptoms. Therefore, there is increasing interest in removing these toxins from the marine environment to protect shellfish harvesting sites. Photocatalysis is proposed as an efficient method to detoxify the marine environment. In this study, Prorocentrum lima was used to produce high purity DSP toxins, in particular OA, for degradation studies. The profiling, characterization and quantification of DSP toxins in the culture of P. lima were achieved by ultrahigh performance liquid chromatography coupled to quadrupole-time of flight mass spectrometry (UPLC-QTOF-MSE) for accurate-mass full spectrum acquisition data. The effectiveness of UV/TiO2 system to degrade OA in seawater was assessed in lab-scale experiments and identification of transformation products was proposed based on the data obtained during analysis by UPLC-QTOF-MSE. The detoxification potential of the UV/TiO2 system was investigated using the phosphatase inhibition assay. Sufficient amount of high-purity OA (25 mg, >90% purity) was produced in-house for use in photocatalysis experiments by simple reversed-phase flash chromatography. Complete degradation of OA was observed in seawater after 30 min and 7.5 min in deionized water. The rate constants fitted with the pseudo-first order kinetic model (R2>0.96). High-resolution mass spectrometry analysis of the photocatalyzed OA allowed tentative identification of four transformation products. Detoxification was achieved in parallel with the degradation of OA in deionized water and artificial ocean water (≤ 20 min) but not for seawater. Overall, results suggest that UV/TiO2 photocatalysis can be an effective approach for degrading OA and their TPs in the marine environment. To the best of our knowledge, this is the first report on the use of photocatalysis to degrade marine toxins and its promising potential to protect shellfish harvesting sites

Stereoselective LC-MS/MS methodologies for environmental analysis of chiral pesticides.

Chiral pesticides can exert stereospecific toxicity in contaminated environmental compartments. Therefore, measuring pesticides at the enantiomeric level is essential to assess the risk posed to exposed organisms, including humans. In recent years, there has been rapid progress on the development and application of stereoselective liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodologies for monitoring pesticides in the environment. Coupling chiral LC separations with MS/MS detection enables trace enantiomeric determination of pesticides in complex environmental matrices. The intent of this review is to provide an up-to-date synopsis on recent advances of stereoselective LC-MS/MS methodologies for pesticide analysis. Key aspects of these methodologies discussed include sample storage and extraction method, stationary phases for separation, multi-residue separations, and method of quantitation. Finally, future trends in this rapidly growing field of analytical chemistry research are outlined

Stereoselective LC-MS/MS methodologies for environmental analysis of chiral pesticides

Chiral pesticides can exert stereospecific toxicity in contaminated environmental compartments. Therefore, measuring pesticides at the enantiomeric level is essential to assess the risk posed to exposed organisms, including humans. In recent years, there has been rapid progress on the development and application of stereoselective liquid chromatography–tandem mass spectrometry (LC–MS/MS) methodologies for monitoring pesticides in the environment. Coupling chiral LC separations with MS/MS detection enables trace enantiomeric determination of pesticides in complex environmental matrices. The intent of this review is to provide an up-to-date synopsis on recent advances of stereoselective LC–MS/MS methodologies for pesticide analysis. Key aspects of these methodologies discussed include sample storage and extraction method, stationary phases for separation, multi-residue separations, and method of quantitation. Finally, future trends in this rapidly growing field of analytical chemistry research are outlined

Enantiomeric profiling of chiral pharmacologically active compounds in the environment with the usage of chiral liquid chromatography coupled with tandem mass spectrometry.

The issue of drug chirality is attracting increasing attention among the scientific community. The phenomenon of chirality has been overlooked in environmental research (environmental occurrence, fate and toxicity) despite the great impact that chiral pharmacologically active compounds (cPACs) can provoke on ecosystems. The aim of this paper is to introduce the topic of chirality and its implications in environmental contamination. Special attention has been paid to the most recent advances in chiral analysis based on liquid chromatography coupled with mass spectrometry and the most popular protein based chiral stationary phases. Several groups of cPACs of environmental relevance, such as illicit drugs, human and veterinary medicines were discussed. The increase in the number of papers published in the area of chiral environmental analysis indicates that researchers are actively pursuing new opportunities to provide better understanding of environmental impacts resulting from the enantiomerism of cPACs

High value phycotoxins from the dinoflagellate Prorocentrum.

Marine dinoflagellates produce chemically diverse compounds, with a wide range of biological activity (antimicrobial, anticancer, treatment of neurodegenerative disease along with use as biomedical research tools). Chemical diversity is highlighted by their production of molecules such as the saxitoxin family of alkaloids (C10H17N7O4 - 299 g/mol) to the amphipathic maitotoxin (C164H256O68S2Na2 - 3,422 g/mol), representing one of the largest and most complex secondary metabolites characterised. Dinoflagellates, are most well-known for the production of red tides which are frequently toxic, including okadaic acid and related dinophysistoxins, which are tumour promoters. The mode of action for these phycotoxins, is by specific inhibition of protein phosphatases, enzymes essential in regulation of many cellular processes. Hence, these compounds are being used for vital cell regulation studies. However, the availability of useful amounts of these compounds has restricted research. Chemical synthesis of some compounds such as okadaic acid has been investigated, but the complexity of the molecule resulted in many lengthy steps and achieved only a poor yield. The use of naturally occurring phytoplankton has been investigated as a potential source of these compounds, but it has been shown to be unreliable and impractical. The most practical option is large scale culture with down-stream processing/purification which requires specialist facilities and expertise. This review, describes the biotechnological potential of these organisms and the challenges to achieve useful yields of high quality phycotoxins using Prorocentrum spp. as an example to produce okadaic acid

Enantioselective LC-MS/MS for anthropogenic markers of septic tank discharge.

Households in rural locations utilize septic tanks for wastewater treatment and can cause surface water contamination. A new methodology was developed to help investigate the role septic tanks play in the dissemination of prescription and over-the-counter drugs, personal care products and stimulants in the aqueous environment. Simultaneous analysis of 16 chiral and achiral anthropogenic markers was achieved using a Chirobiotic V2® enantioselective column in polar ionic mode. The optimized method achieved quantitation limits for 16 compounds in the range 0.001–2.9 μg L−1 and 0.0002–0.43 μg L−1 for septic tank effluent and stream water, respectively. Application of the method to samples collected in North East Scotland found caffeine to be ubiquitous in all samples studied suggesting it as a good indicator of septic tank discharge. In rural streams studied, concentrations of all prescription drugs investigated were ≤0.02 μg L−1. However, analgesics and stimulants were at high concentration in one location indicating direct discharge of septic tank wastewater (i.e., not dissipated through a soak away). For example, paracetamol, cotinine and caffeine were measured at 1100 μg L−1, 31 μg L−1 and 200 μg L−1, respectively, which is comparable to septic tank effluents. Furthermore, S(+)-amphetamine and R(−)-amphetamine were present in this stream sample at 0.20 and 0.27 μg L−1. This corresponds to an enantiomeric fraction of 0.43, which is typical of untreated wastewaters in the UK. Findings illustrate further study on the diffuse impact of septic tanks to surface water is needed and can be supported using this new multi-residue enantioselective method

Edición de encuestas mediante redes de neuronas artificiales

Se presenta un procedimiento de imputación de valores perdidos y un método para la detección y corrección de inconsistencias en las respuestas recogidas como resultado de una encuesta estadística. Para ello se describe el Perceptrón Multinivel, modelo concreto de Redes de Neuronas Artificiales utilizado en nuestro trabajo, y se ilustra el funcionamiento del procedimiento sobre la cuestión “Intención de voto” de una encuesta electoral del Centro de Investigaciones Sociológicas. Sobre estos datos reales, la técnica de imputación construída se basa en un modelo de predicción de la intención de voto a partir de las demás cuestiones, presentando una capacidad de generalización estimada que puede calificarse de perfecta. El modelo de detección y corrección de inconsistencias ofrece un rendimiento bastante satisfactorio, por lo que el perceptrón multinivel, confirmando algunos trabajos existentes con datos simulados, se puede considerar como un método prometedor en las tareas de edición de los registros resultantes de una encuesta estadística.Instituto de Estadística de Andalucí

Solar-driven semi-conductor photocatalytic water treatment (TiO2, g-C3N4, and TiO2+g-C3N4) of cyanotoxins: proof-of-concept study with microcystin-LR.

Cyanobacteria and their toxins are a threat to drinking water safety as increasingly cyanobacterial blooms (mass occurrences) occur in lakes and reservoirs all over the world. Photocatalytic removal of cyanotoxins by solar light active catalysts is a promising way to purify water at relatively low cost compared to modifying existing infrastructure. We have established a facile and low-cost method to obtain TiO2 and g-C3N4 coated floating photocatalysts using recycled glass beads. g-C3N4 coated and TiO2+g-C3N4 co-coated beads were able to completely remove microcystin-LR in artificial fresh water under both natural and simulated solar light irradiation without agitation in less than 2 h. TiO2 coated beads achieved complete removal within 8 h of irradiation. TiO2+g-C3N4 beads were more effective than g-C3N4 beads as demonstrated by the increase reaction rate with reaction constants, 0.0485 min−1 compared to 0.0264 min−1 respectively, with TiO2 alone found to be considerably slower 0.0072 min−1. g-C3N4 based photocatalysts showed a similar degradation pathway to TiO2 based photocatalysts by attacking the C6–C7 double bond on the Adda side chain