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This study investigates the pilot-scale ozone treatment of reverse osmosis concentrate (ROC), originating from variable tank truck cleaning wastewater. The influence of ozonation on short- and long-term biodegradation potential was examined through respirometry and Zahn-Wellens, respectively. Ecotoxicity was also examined for several concentrate batches and ozonation steps. Chemical oxidation through ozone had a beneficial effect on chemical oxygen demand removal, with a removal efficiency up to 56%. Formation of short-term biochemical oxygen demand (BODst) was induced for several, but not all batches, showing the potential of subsequent biological treatment of ozonated ROC. An increase in the inherent biodegradability through Zahn-Wellens was observed for all tested samples after ozonation, rising to a maximum of 68% after 3 hours of ozonation, highlighting the importance of sludge adaptation. Ecotoxicity, tested with Artemia franciscana and the saltwater algae P. tricornutum, showed initial decreases in algae inhibition after short ozonation periods. An increase in algae inhibition was, however, seen after prolonged ozonation for all tested ROC samples, pointing to the formation of ecotoxic by-products. Artemia showed no significant toxicity effects. When applying biological treatment through Zahn-Wellens, a decrease in ecotoxicity was observed for several samples, likely through biological oxidation of the produced degradation products. ispartof: WATER SCIENCE AND TECHNOLOGY vol:87 issue:1 pages:1-12 ispartof: location:England status: published

ispartof: Chemical Engineering Journal vol:449 status: Published online

Intra-particle diffusion is investigated in particle-packed and monolithic zwitterionic hydrophilic interaction liquid chromatography (HILIC) polymer columns. For this purpose, plate heights are first measured over a broad range of velocities for polar compounds with zone retention factors between k″ = 2 and 10 on all column types, multiplied with the corresponding velocity, and extrapolated to zero velocity. The thus obtained B-term coefficients are additionally verified via peak parking experiments and indicate a very low degree of longitudinal diffusion in all columns, that moreover seems to be independent of the zone retention factor. This is in contrast to earlier observations on reversed-phase liquid chromatography columns and bare silica HILIC columns. To obtain more insight into the reasons for these low levels of longitudinal diffusion, the experimentally obtained effective diffusion coefficients are modeled to equations derived from the effective medium theory, such as the models developed by Torquato and Jefrey & Hashin. It is, however, demonstrated that these models fail to adequately describe effective diffusion in the studied zwitterionic HILIC columns, due to the low degree of intraparticle diffusion in these stationary phases. Fitting the experimental effective diffusion coefficients to the two limiting cases of the effective medium theory, i.e., the pure parallel-connection and pure serial-connection case, it is observed that to stay within these limits, intraparticle diffusion must be extremely low, i.e., Dpz/Dm ≤ 0.01, indicating that the diffusion inside the pores is at least 100 times smaller than the bulk diffusion coefficient. There are several possible explanations for these low intraparticle diffusion coefficients, such as a strongly hindered diffusion in the polymer matrix, extremely low surface diffusion rates in the aqueous layer adsorbed onto the stationary phase and/or the occurrence of slow localized adsorption events.

The present study investigates the kinetics and mechanisms of carbamazepine (CBZ) degradation using a novel UV/iodate (IO3-) system for the first time and explores the influence of process conditions on its degradation. UV/IO3- showed high degradation efficiencies in a wide range of pHs, especially under neutral and acidic conditions, indicating that the system can be considered as a promising method to deal with effluents under various pH conditions. Radical scavenging experiments show that both iodine radicals (IO, IO2 and IO3) and hydroxyl radicals play an important role in CBZ degradation. Furthermore, the combination of UV/IO3- with TiO2 was studied to explore the potential of the addition of IO3- to improve the efficiency of the conventional TiO2 photocatalytic system. Scavenging experiments indicated that iodine radicals (IO, IO2 and IO3) were mainly involved in the degradation of CBZ in the UV/IO3-/TiO2 system, and the reaction mechanism equations were proposed for the first time for the studied UV/IO3-/TiO2 system. Several degradation products and four possible pathways of CBZ degradation were also elucidated using ultra-high-performance liquid chromatography in combination with a quadrupole time-of-flight mass spectrometer (Q-TOF MS). Respirometric tests indicated that the treatment has a positive impact on biomass behavior during subsequent biological purification, highlighting that the developed IO3--assisted AOPs are eco-friendly. published

Although commercially available software provides options for automatic peak detection, visual inspection and manual corrections are often needed. Peak detection algorithms commonly employed require carefully written rules and thresholds to increase true positive rates and decrease false positive rates. In this study, a deep learning model, specifically, a convolutional neural network (CNN), was implemented to perform automatic peak detection in reversed-phase liquid chromatography (RPLC). The model inputs a whole chromatogram and outputs predicted locations, probabilities, and areas of the peaks. The obtained results on a simulated validation set demonstrated that the model performed well (ROC-AUC of 0.996), and comparably or better than a derivative-based approach using the Savitzky-Golay algorithm for detecting peaks on experimental chromatograms (8.6% increase in true positives). In addition, predicted peak probabilities (typically between 0.5 and 1.0 for true positives) gave an indication of how confident the CNN model was in the peaks detected. The CNN model was trained entirely on simulated chromatograms (a training set of 1,000,000 chromatograms), and thus no effort had to be put into collecting and labeling chromatograms. A potential major drawback of this approach, namely training a CNN model on simulated chromatograms, is the risk of not capturing the actual "chromatogram space" well enough that is needed to perform accurate peak detection in real chromatograms.

Dravet syndrome (DS) is a rare genetic encephalopathy that is characterized by severe seizures and highly resistant to commonly used antiepileptic drugs (AEDs). In 2020, FDA has approved fenfluramine (FFA) for treatment of seizures associated with DS. However, the clinically used FFA is a racemic mixture (i.e. (±)-FFA), that is substantially metabolized to norfenfluramine (norFFA), and it is presently not known whether the efficacy of FFA is due to a single enantiomer of FFA, or to both, and whether the norFFA enantiomers also contribute significantly. In this study, the antiepileptic activity of enantiomers of FFA (i.e. (+)-FFA and (−)-FFA) and norFFA (i.e. (+)-norFFA and (−)-norFFA) was explored using the zebrafish scn1Lab−/− mutant model of DS. To validate the experimental conditions used, we assessed the activity of various AEDs typically used in the fight against DS, including combination therapy. Overall, our results are highly consistent with the treatment algorithm proposed by the updated current practice in the clinical management of DS. Our results show that (+)-FFA, (−)-FFA and (+)-norFFA displayed significant antiepileptic effects in the preclinical model, and thus can be considered as compounds actively contributing to the clinical efficacy of FFA. In case of (−)-norFFA, the results were less conclusive. We also investigated the uptake kinetics of the enantiomers of FFA and norFFA in larval zebrafish heads. The data show that the total uptake of each compound increased in a time-dependent fashion. A somewhat similar uptake was observed for the (+)-norFFA and (−)-norFFA, implying that the levo/dextrotation of the structure did not dramatically affect the uptake. Significantly, when comparing (+)-FFA with the less lipophilic (+)-norFFA, the data clearly show that the nor-metabolite of FFA is taken up less than the parent compound.

Biopharmaceuticals are administered parenterally and therefore sterility is required. Sterility can be obtained via different processes including exposure to steam or dry heat. Sterilisation studies on biopharmaceuticals, which are highly sensitive medicinal products, are scarce. This study investigates the effect of different sterilisation processes on recombinant human insulin in solid state (gamma and e-beam irradiation (w/wo dry ice), nitrogen dioxide (NO2)) and in aqueous solution (gamma irradiation (w/wo dry ice, w/wo glycerin)) using ultra-high performance liquid chromatography-diode array detection-mass spectrometry. It is observed that NO2 substantially degrades the solid samples, while gamma and e-beam irradiation result in lower levels of degradation (mean normalized peak areas of 95.2-96.2 % with respect to the non-sterilised samples). Gamma irradiation of insulin solutions with and without dry ice at 2.5 kGy results in mean normalised peak areas of 85 % and

High-Performance Liquid Chromatography (HPLC) is a key technique in the evaluation of biopharmaceuticals. To improve the separation of biopharmaceuticals, it is crucial to improve the fundamental understanding of the parameters governing their band broadening behavior. This can be obtained by a detailed assessment of the individual contributions to their mass transfer. For this purpose, a precise knowledge of the molecular diffusion coefficient (Dm) of biopharmaceuticals is required. Only little experimental data is available for the Dm-values of biopharmaceuticals under HPLC relevant conditions. Furthermore, none of the available equations that can be used to calculate Dm-values, allows to account for any conformational changes that might occur. The Taylor-Aris method is a very simple and absolute method that is often employed to determine Dm-coefficients. The Taylor-Aris method measures the band broadening of an analyte in an open tube under laminar conditions, wherein (1) longitudinal diffusion can be ignored, (2) the sample is fully radially equilibrated and (3) the contribution of the extra-column variance to the total variance is negligible. Moreover, since the open tubes are typically coiled for practical reasons, (4) the influence of secondary flows on the band broadening should be insignificant. In this tutorial paper, the impact of the four conditions mentioned above on the accuracy of the obtained Dm values is revisited. For this purpose, Dm values are measured for two representative compounds (Bovine Serum Albumin and Thiourea), and the obtained values are compared with literature data and theoretical recommendations. Based on these observations, a set of 'rules' for accurate and fast Dm measurements is put forward. Finally, an Interactive Tool (IT), combining these rules in a comprehensive way, is introduced and can be used to set up TA experiments. ispartof: JOURNAL OF CHROMATOGRAPHY A vol:1664 ispartof: location:Netherlands status: published

In this study, CuO was synthesized using a facile precipitation method and was characterized using various techniques for the efficient activation of periodate (PI). Compared to systems consisting of PI alone (0.5 mM) and CuO alone (0.5 g/L), the CuO (0.5 g/L)/PI (0.5 mM) process exhibited improved degradation performance for ciprofloxacin (CIP), a widely used refractory antibacterial drug, with 98% of this pollutant (20 mg/L) removed in a reaction time of 30 min. Both radical and nonradical degradation pathways were identified to play a significant role in the developed CuO/PI system, where the nonradical pathway (holes and electrons) played the most important role in the degradation of CIP. Under both acidic (pH = 3) and near-neutral (pH = 6) conditions, the system showed an improved efficiency for the degradation of CIP in comparison with alkaline conditions (pH = 10). This was attributed to a more facile adsorption of the PI ions onto the surface of the CuO nanoparticles, induced by the electrostatic attraction between the PI ions and the CuO nanomaterial. Analysis of the degraded samples with ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC Q-TOF MS) demonstrated that cleavage of the piperazine ring and defluorination were the primary degradation pathways of CIP under this oxidation process. The CuO/PI system also showed an excellent removal efficiency for other refractory organic contaminants, such as sulfamethoxazole (SMX) and methylene blue (MB), in various water matrices, including real wastewater. Moreover, respiration tests revealed that the toxicity of the effluents was reduced after the treatment process. In conclusion, this research presents a novel, promising periodate activation technique for the removal of refractory organic contaminants in wastewater treatment.

Machine learning is a popular technique to predict the retention times of molecules based on descriptors. Descriptors and associated labels (e.g., retention times) of a set of molecules can be used to train a machine learning algorithm. However, descriptors are fixed molecular features which are not necessarily optimized for the given machine learning problem (e.g., to predict retention times). Recent advances in molecular machine learning make use of so-called graph convolutional networks (GCNs) to learn molecular representations from atoms and their bonds to adjacent atoms to optimize the molecular representation for the given problem. In this study, two GCNs were implemented to predict the retention times of molecules for three different chromatographic data sets and compared to seven benchmarks (including two state-of-the art machine learning models). Additionally, saliency maps were computed from trained GCNs to better interpret the importance of certain molecular sub-structures in the data sets. Based on the overall observations of this study, the GCNs performed better than all benchmarks, either significantly outperforming them (5-25% lower mean absolute error) or performing similar to them (

The origin of the peak skewness that can be observed when applying the deconvolution method to isolate the diffusion process from the flow processes for peak parking experiments conducted under conditions of slow radial equilibration and strong trans-column velocity gradients was investigated. Numerical simulations were carried out for a variety of trans-column velocity profiles and a broad range of experimental conditions and system parameters were investigated. Results show that, under the aforementioned conditions, the traditionally employed variance subtraction method displays a consistent error which follows the dynamics of the diffusive relaxation during both the peak parking and the flow steps. It is also found that, under the same conditions, the peak deconvolution method is bound to produce deconvoluted "parking-only" peaks that are strongly asymmetric, despite the perfectly symmetric nature of the pure diffusion process marking this parking step. It is shown that this asymmetry is acquired during the flow step following the parking stop. During this step, parked and non-parked peaks are deformed in different ways, despite being subjected to the same trans-column velocity profile. This different deformation cannot be filtered away with the deconvolution or the variance subtraction method, hence introducing an error. Solutions to alleviate the peak skewness and the variance error consist of parking the peak close to the inlet or the outlet or exiting the parked peak through the column inlet (flow reversal method). Under the considered conditions, these approaches could reduce the error on the measured effective diffusion coefficient up to 87%. Carrying out the variance subtraction or the deconvolution process with a peak that has also been parked for a substantially long parking time instead of using a "no-parking" peak as is customary done, is another option to counter the effect. ispartof: JOURNAL OF CHROMATOGRAPHY A vol:1656 ispartof: location:Netherlands status: published

Zebrafish (Danio rerio) is increasingly used to assess the pharmacological activity and toxicity of compounds. The spatiotemporal distribution of seven fluorescent alkyne compounds was examined during 48 h after immersion (10 µM) or microinjection (2 mg/kg) in the pericardial cavity (PC), intraperitoneally (IP) and yolk sac (IY) of 3 dpf zebrafish eleuthero-embryos. By modelling the fluorescence of whole-body contours present in fluorescence images, the main pharmacokinetic (PK) parameter values of the compounds were determined. It was demonstrated that especially in case of short incubations (1-3 h) immersion can result in limited intrabody exposure to compounds. In this case, PC and IP microinjections represent excellent alternatives. Significantly, IY microinjections did not result in a suitable intrabody distribution of the compounds. Performing a QSPkR (quantitative structure-pharmacokinetic relationship) analysis, LogD was identified as the only molecular descriptor that explains the final uptake of the selected compounds. It was also shown that combined administration of compounds (immersion and microinjection) provides a more stable intrabody exposure, at least in case of a prolonged immersion and compounds with LogD value > 1. These results will help reduce the risk of false negative results and can offer an invaluable input for future translational research and safety assessment applications. ispartof: SCIENTIFIC REPORTS vol:11 issue:1 ispartof: location:England status: published

Diclofenac (DCF) is a non-steroidal anti-inflammatory drug which is frequently detected in the aqueous environment. The synergistic treatment using sulfite and UV irradiation is proposed to be one of the most effective advanced reduction processes (ARPs) to degrade refractory contaminants. This paper systematically investigated the performance and mechanism of DCF degradation by sulfite/UV ARP under various conditions. A significant enhancement in degradation efficiency of DCF was exhibited via sulfite/UV ARP compared with direct UV photolysis, which is primarily due to the generation of reductive radicals (eaq− and H ). This process was well described by a pseudo first-order kinetic model with a rate constant of 0.154 min−1. The influence of solution pH, sulfite dosage, initial DCF concentration and UV intensity were evaluated. Results revealed that DCF more favorably reacted with H in an acidic environment than with eaq− under alkaline conditions. A positive impact on the DCF decomposition was observed with increasing sulfite dosage, but with an inhibiting trend at high sulfite concentrations. The degradation rate constant was accelerated by increasing the UV intensity, while decreased by promoting the initial DCF concentration. Degradation mechanisms at different pH levels revealed that the reduction reactions were induced by eaq− at pH 9.2, and dominated by H at pH 6.0. Complete dechlorination was readily achieved with all chlorine atoms in DCF released as chloride ions under sulfite/UV ARP, which may lead to a decreased toxicity of the degradation products. This observation emphasized the advantages of sulfite/UV ARP on DCF degradation, in comparison with that under direct UV photolysis.

In this contribution, we review the recent literature relating to the measurement and modelling of all diffusion-dominated processes contributing to the efficiency of a chromatographic column. In first instance, this involves the measurement and modelling of the overall effective diffusion coefficient Deff (determining the so-called B-term band broadening). The latter manifests itself most clearly during a so-called peak parking experiment. Using effective medium theory modelling, the measured Deff-value can subsequently be decomposed into its constituent contributions, of which the intra-particle or the mesoporous zone and the surface diffusion coefficient are the most important ones. As an accurate estimation of the diffusion processes also allows computing the C-term plate height contribution terms, the review ends with some recent insights obtained when using the established B- and C-term contributions to compute the degree of eddy-dispersion in contemporary packed bed columns.

Enhancement of chromatograms, such as the reduction of baseline noise and baseline drift, is often essential to accurately detect and quantify analytes in a mixture. Current methods have been well studied and adopted for decades and have assisted researchers in obtaining reliable results. However, these methods rely on relatively simple statistics of the data (chromatograms) which in some cases result in significant information loss and inaccuracies. In this study, a deep one-dimensional convolutional autoencoder was developed that simultaneously removes baseline noise and baseline drift with minimal information loss, for a large number and great variety of chromatograms. To enable the autoencoder to denoise a chromatogram to be almost, or completely, noise-free, it was trained on data obtained from an implemented chromatogram simulator that generated 190.000 representative simulated chromatograms. The trained autoencoder was then tested and compared to some of the most widely used and well-established denoising methods on testing datasets of tens of thousands of simulated chromatograms; and then further tested and verified on real chromatograms. The results show that the developed autoencoder can successfully remove baseline noise and baseline drift simultaneously with minimal information loss; outperforming methods like Savitzky-Golay smoothing, Gaussian smoothing and wavelet smoothing for baseline noise reduction (root mean squared error of 1.094 mAU compared to 2.074 mAU, 2.394 mAU and 2.199 mAU) and Savitkzy-Golay smoothing combined with asymmetric least-squares or polynomial fitting for baseline noise and baseline drift reduction (root mean absolute error of 1.171 mAU compared to 3.397 mAU and 4.923 mAU). Evidence is presented that autoencoders can be utilized to enhance and correct chromatograms and consequently improve and alleviate downstream data analysis, with the drawback of needing a carefully implemented simulator, that generates realistic chromatograms, to train the autoencoder. ispartof: JOURNAL OF CHROMATOGRAPHY A vol:1646 ispartof: location:Netherlands status: published

The presence of nonylphenol (NP) in the wastewater of the tank truck cleaning industry is a major concern because of its endocrine disruptive properties. In this paper, the use of ozone for degrading NP from tank truck cleaning wastewater was investigated by operating a pilot-scale biological wastewater treatment in combination with an ozonation unit. The impact of the added ozonation step on the removal of NP, soluble chemical oxygen demand (sCOD) and total organic carbon (TOC) was monitored over one year. sCOD and TOC removal were not significantly enhanced, but the NP peak concentrations in the effluent were significantly lower than those obtained after biological treatment only: a relatively low NP concentration was observed, even when peak loads were present in the influent of the pilot-scale biological wastewater treatment plant (influentbio). Contrariwise, the effluent of the sole biological treatment follows the peak load trends of the influentbio. During the ozonation period, the average NP concentration in the combined biological-ozone unit was 0.29 μg/L, compared to 1.89 μg/L for the effluent obtained after a sole biological treatment, resulting in an improved average removal efficiency of 32%. ispartof: JOURNAL OF ENVIRONMENTAL MANAGEMENT vol:288 ispartof: location:England status: published

ispartof: JOURNAL OF CHROMATOGRAPHY A vol:1642 ispartof: location:Netherlands status: published

An important challenge in chromatography is the development of adequate separation methods. Accurate retention models can significantly simplify and expedite the development of adequate separation methods for complex mixtures. The purpose of this study was to introduce reinforcement learning to chromatographic method development, by training a double deep Q-learning algorithm to select optimal isocratic scouting runs to generate accurate retention models. These scouting runs were fit to the Neue-Kuss retention model, which was then used to predict retention factors both under isocratic and gradient conditions. The quality of these predictions was compared to experimental data points, by computing a mean relative percentage error (MRPE) between the predicted and actual retention factors. By providing the reinforcement learning algorithm with a reward whenever the scouting runs led to accurate retention models and a penalty when the analysis time of a selected scouting run was too high (> 1h); it was hypothesized that the reinforcement learning algorithm should by time learn to select good scouting runs for compounds displaying a variety of characteristics. The reinforcement learning algorithm developed in this work was first trained on simulated data, and then evaluated on experimental data for 57 small molecules – each run at 10 different fractions of organic modifier (0.05 to 0.90) and four different linear gradients. The results showed that the MRPE of these retention models (3.77% for isocratic runs and 1.93% for gradient runs), mostly obtained via 3 isocratic scouting runs for each compound, were comparable in performance to retention models obtained by fitting the Neue-Kuss model to all (10) available isocratic datapoints (3.26% for isocratic runs and 4.97% for gradient runs) and retention models obtained via a “chromatographer's selection” of three scouting runs (3.86% for isocratic runs and 6.66% for gradient runs). It was therefore concluded that the reinforcement learning algorithm learned to select optimal scouting runs for retention modeling, by selecting 3 (out of 10) isocratic scouting runs per compound, that were informative enough to successfully capture the retention behavior of each compound. ispartof: Journal Of Chromatography A vol:1638 ispartof: location:Netherlands status: published

This study explores the efficiency and kinetics of the photoactivated periodate process for the degradation of 2,4-dichlorophenol (2,4-DCP) in water. The obtained results show that the degradation rate was considerably higher for UV/IO

In an ongoing effort to better understand the underlying mechanisms of band broadening in particle-packed reversed-phase liquid chromatography columns, new models for intra-particle diffusion, representing an adsorption- and partition-type retention behavior, are proposed. These models assume the mesoporous zone inside the particles is subdivided in four distinct regions: a fraction f1 filled with bulk mobile phase, a fraction f2 enriched in pure organic modifier extending outside the stationary phase layer, a fraction f3 comprising the liquid surrounding the alkyl chains and a fraction f4 consisting of the stationary phase alkyl chains. Intra-particle diffusion is calculated as a residence time weighted average of the diffusion in these different regions. Experimental procedures and models are proposed to determine the volumes of these four regions and applied to three reversed-phase liquid chromatography columns with different pore sizes (80 Å versus 300 Å) and different stationary phase types (C18 versus C8). The newly proposed models are then applied to predict the intra-particle diffusion of butyrophenone across a wide range of retention factors (1 ≤ k" ≤ 40) in each of these columns. These predictions are compared to experimental data that are extracted from the effective diffusion coefficients of butyrophenone obtained via peak parking experiments. It is demonstrated that both adsorption- and partition-type models for intra-particle diffusion model the actual behavior of the test compound well, and require the determination of only one (partition) or two (adsorption) fitting factors: the obstruction to free movement the analytes experience from the alkyl chains in the retained state (partition and adsorption) and in the unretained state (adsorption). Finally, it is demonstrated that the major contributor to the intra-particle diffusion of retained compounds (k" > 2) is the diffusion these analytes undergo when retained in the organic-modifier enriched zone surrounding the alkyl chains (partition model) or when adsorbed onto the alkyl chains (adsorption model), confirming that surface diffusion plays an important role in the mass transfer of retained compounds in reversed-phase liquid chromatography columns. ispartof: JOURNAL OF CHROMATOGRAPHY A vol:1637 ispartof: location:Netherlands status: published

In this study, the degradation of ciprofloxacin (CIP) in wastewater was investigated using UV-based sulfate radical advanced oxidation processes (SR-AOP) and UV-based advanced reduction processes (ARP). More specifically, a comparison of the UV-based persulfate advanced oxidation process (the UV/PS process) and the UV-based sulfite advanced reduction process (the UV/sulfite process) was made. Considering the UV-based SR-AOPs, the UV/PS process was much more efficient than the UV-based peroxymonosulfate advanced oxidation process (the UV/PMS process), with pseudo first order reaction rate constants (kobs) of 0.752 and 0.145 min-1, respectively. For the UV-based ARPs, the UV/sulfite process was the most efficient, compared to the UV/sulfide and the UV/dithionite process (kobs of 0.269, 0.0157 and 0.0329 min-1, respectively). The optimal process parameters for both the UV/PS and the UV/sulfite process were determined and the contribution of the produced reactive species were identified. For the UV/PS process, maximal CIP degradation was found at pH 8, and both OH and SO4- were responsible for CIP degradation. For the UV/sulfite process, H and eaq- were responsible for CIP degradation, with eaq- being the predominant radical at pH 8.5. Although CIP degradation was much faster for the UV/PS process, the UV/sulfite process was determined to be much more efficient in the defluorination of CIP. ispartof: SCIENCE OF THE TOTAL ENVIRONMENT vol:764 ispartof: location:Netherlands status: published

The aim of this study was to predict the residual adsorbable organic halides (AOX) concentration in an industrial wastewater using conventional, easy-to-measure wastewater parameters. In a pilot test unit, the wastewater was subjected to ozonation at various intensities, resulting in an AOX-removal and hence varying AOX concentrations. In first instance, the parameters used for modeling were selected using Pearson and Spearman correlations. Secondly, multiple linear regression (MLR) was used as a modeling tool to predict both the soluble and total AOX concentration in wastewater samples. To prevent overfitting, a 10-fold cross-validation was carried out. It was found that both the soluble and the total AOX concentration can be predicted using typical wastewater parameters. The measured parameters were pH, chloride concentration, Water-Soluble Organic Carbon concentration (WSOC), UV-VIS spectrum, turbidity, and Solids Removable by Filtration (SRF). Out of these parameters, the following parameters were found to be significant for prediction of the total AOX concentration: turbidity, SRF, UV-VIS absorbance at 200, 227, and 250 nm, and pH. UV-VIS absorbance at 200 and 227 nm and turbidity of the wastewater were found to contribute significantly to the final model. For the soluble AOX concentration, the significant parameters were turbidity, absorbance at 200, 227, and 250 nm, pH, and chloride concentration. Here, UV-VIS absorbance at 200 and 227 nm were found to contribute significantly to the final model. The obtained final models had an adjusted R2 of 0.921 and 0.916 for the total and soluble AOX, respectively. As a result of the obtained models, both AOX concentrations can be predicted using parameters that are easier to determine. This allows for a significant reduction in wastewater sampling and analysis time and offers the opportunity to optimize the ozone dosing in the wastewater treatment process in the future.

An LC-MS/MS method was developed enabling the separation and quantification of histamine and its main metabolites (imidazole acetaldehyde, imidazole acetic acid, methyl imidazole acetic acid, methyl histamine, acetyl histamine) in urine samples. A fast separation was achieved in 10 min on two HILIC columns connected in series by adopting a linear gradient followed by an isocratic hold. The sample preparation consisted of a simple dilution step wherein 10 μL of urine was diluted with acetonitrile (ACN) to a final volume comprising 95% ACN. For methyl imidazole acetic acid, an additional dilution step was incorporated due to its high natural levels. Hereafter, the samples were stored at -20 °C and centrifuged prior to injection. Matrix matched calibrators were unavailable due to the endogenous occurrence of the compounds of interest. The occurrence of matrix effects and the lack of labeled internal standards prompted the use of the standard addition method as a viable alternative to solvent calibration. The validation of the method entailed matrix effects, accuracy and precision and was performed in compliance with the recent guidelines on endogenous compounds issued by the International Conference of Harmonization (ICH). The method was then adopted for the quantification of histamine and its metabolites in human urine samples collected from healthy volunteers and patients suffering from gastrointestinal discomfort. ispartof: TALANTA vol:220 ispartof: location:Netherlands status: published

Up to 20% of people worldwide develop gastrointestinal symptoms following a meal(1), leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response that leads to the production of dietary-antigen-specific IgE antibodies in mice, which are limited to the intestine. Following subsequent oral ingestion of the respective dietary antigen, an IgE- and mast-cell-dependent mechanism induced increased visceral pain. This aberrant pain signalling resulted from histamine receptor H-1-mediated sensitization of visceral afferents. Moreover, injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid mucosa of patients with irritable bowel syndrome induced local oedema and mast cell activation. Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders. In mice, oral tolerance to food antigens can break down after enteric infection, and this leads to food-induced pain resembling irritable bowel syndrome in humans.

An experimental methodology for the determination of the obstruction factor in the expression for mesopore diffusion in Zorbax Eclipse Plus C-18 reversed-phase particles is proposed. The method uses peak parking experiments conducted on particles that were previously stripped of their stationary phase by flushing the column with trifluoroacetic acid at a temperature of 60 degrees C. Further using pure organic solvents as the mobile phase, any potential retention or surface diffusion effect is omitted. To avoid interference between the parked peaks and baseline disturbances typically occurring when switching on and off the flow, peak parking experiments were carried out in a set-up wherein two identical columns were used in parallel. This set-up allowed to maintain the flow through the detector at all times, by redirecting the flow from one column to the other during the peak parking experiments. Several tracer molecules (ionic and deuterated tracers) were compared and it was found that the use of deuterated molecules provides the best possible coverage of the accessible space of the mesopore volume. Interpreting the peak parking responses obtained with these tracers with a model based on the effective medium theory (EMT) subsequently provided an estimate of the value of the mesopore diffusion obstruction factor gamma(mp). Taking the well-established pore hindrance factor F(lambda) correction into account, the obtained experimental gamma(mp)- values are more in agreement with the tortuous and constricted diffusion paths one can expect in the void space within a structure resembling a monolithic skeleton with tetrahedral connectivity rather than in the void space formed by a packing of nanospheres. This is also more in line with the measured internal porosity values lying around epsilon(pz) =0.5, whereas a packing of nanospheres would rather correspond to an epsilon(pz) of 0.4. As such, the presented protocol provides a means to infer the internal mesopore structure of reversed-phase particles. (C) 2020 Elsevier B.V. All rights reserved.

Liquid chromatography (LC) based techniques in combination with mass spectrometry (MS) detection have had a large impact on the development of new pharmaceuticals in the past decades. Continuous improvements in mass spectrometry and interface technologies, combined with advanced liquid chromatographic techniques for high-throughput qualitative and quantitative analysis, have resulted in a wider scope of applications in the pharmaceutical field. LC-MS tools are increasingly used to analyze pharmaceuticals across a variety of stages in their discovery and development. These stages include drug discovery, product characterization, metabolism studies (in vitro and in vivo) and the identification of impurities and degradation products. The increase in LC-MS applications has been enormous, with retention times and molecular weights (and related fragmentation patterns) emerging as crucial analytical features in the drug development process. The goal of this review is to give an overview of the main developments in LC-MS based techniques for the analysis of small pharmaceutical molecules in the last decade and give a perspective on future trends in LC-MS in the pharmaceutical field. ispartof: ANALYST vol:145 issue:4 pages:1129-1157 ispartof: location:England status: published

In this article, heat-activated persulfate oxidation was investigated as a promising technique for the removal of sulfamethoxazole from an aqueous environment. It was found that the degradation efficiency of sulfamethoxazole increases with increasing persulfate concentration due to the increased •SO4- production. As suggested by the Arrhenius equation, the sulfamethoxazole degradation rate constant increased with increasing temperature. An activation energy of 103 kJ/mol was determined. Furthermore, the initial pH of the reaction mixture had a large influence on the degradation of sulfamethoxazole. At higher initial pH values, the degradation of sulfamethoxazole increased. The main cause for this increase is a difference in sulfamethoxazole distribution: at higher pH, the deprotonated form of sulfamethoxazole is present and found to be more susceptible to degradation. A second reason was found to be the formation of •OH at higher initial pH values, although this contribution was smaller. To elucidate the degradation process, six intermediates were identified, and the difference in formation of these compounds at different initial pH values was revealed. Through ECOSAR modeling, some degradation products were found to be of main interest when monitoring the toxicity of the degradation mixture. ispartof: Chemical Engineering Journal vol:379 status: Published online

In this research, the activation of peroxymonosulfate (PMS) by ferrous iron (Fe2+) was investigated as a technique for the degradation of sulfamethoxazole (SMX). First, the influence of the Fe2+:PMS molar ratio on the obtained degradation efficiency was investigated and an excess of Fe2+ was found to result in a decrease in SMX degradation efficiency, while, for the investigated molar ratios, an excess of PMS was found to enhance the degradation efficiency. To obtain a higher degradation efficiency, the dosing strategy of the reagents was altered: from direct dosing (introducing the reagents all at once) to sequential dosing (adding the same total amount of reagent, but divided over specific time intervals) and continuous dosing (adding the same total amount of reagent, but continuously over 30 min reaction time). Continuous dosing of both Fe2+ and PMS was found to be the optimal strategy, with a SMX degradation efficiency of 67% in 50 min reaction time. By performing scavenging experiments, the reactive species (•OH, •SO4- and Fe(IV) present in this process were identified. It was found that the contribution of •OH to the degradation of SMX increased when changing from direct to continuous dosing. Lastly, the formed degradation products were identified, and differences in reaction pathway depending on the reactive species present were elucidated.

© 2017 Elsevier B.V. This study assesses the degradation by electrochemical oxidation via boron doped diamond (BDD) electrodes of the selected pharmaceutical compounds iopromide (IOP), sulfamethoxazole (SMX), 17-alpha-ethinylestradiol (EE2) and diclofenac (DCF) in simulated wastewater and real hospital effluent wastewater. The influence of the flow rate in the electrochemical cell, applied current, initial compound concentration and wastewater matrix (simulated (SWW) versus real effluent (RWW) wastewater) was evaluated. A kinetic evaluation confirmed that the degradation can be described via pseudo first-order reaction kinetics for all experimental conditions tested. It was shown that SMX, EE2 and DCF degraded readily in SWW and RWW. The degradation of IOP was significantly slower, which is in agreement with previously reported slow degradation kinetics using typical advanced oxidation processes. Activation energies for the degradation reactions were calculated. The flow rate in the electrochemical cell had only a moderate effect on the degradation rate of EE2 and DCF. The applied current, however, had a major effect. The BDD electrochemical oxidation was shown to be an effective technique for removing pharmaceutical components from the effluent of a biological hospital wastewater treatment plant. However, the slower degradation of transformation products should be taken into account, when a full mineralization of the pharmaceuticals is pursued. ispartof: Separation and Purification Technology vol:195 pages:184-191 status: published

The present study explores the potential of 10-day-old zebrafish (Danio rerio) as a predictive blood-brain-barrier model using a set of 7 pharmaceutical agents. For this purpose, zebrafish were incubated with each of these 7 drugs separately via the route of immersion and the concentration reaching the brain was determined by applying a brain extraction procedure allowing isolation of the intact brain from the head of the zebrafish larvae. Sample analysis was performed utilizing capillary ultra-high performance liquid chromatography (cap-UHPLC) on a Pepmap RSLC C18 capillary column (150 mm × 300 μm, dp = 2 μm) coupled to a variable wavelength UV detector. Gradient separation was performed in 28 min at a flow rate of 5 μL/min and the optimal injection volume was determined to be 1 μL. The brain extraction procedure was established for the zebrafish strain TG898 exhibiting red fluorescence of the brain, allowing control of the integrity of the extracted parts. Quantitative experiments carried out on pooled samples of six zebrafish (n = 6) demonstrated the selective semipermeable nature of the blood-brain barrier after incubating the zebrafish at the maximum tolerated concentration for the investigated pharmaceuticals. The obtained brain-to-trunk ratios ranged between 0.3 for the most excluded compound and 1.2 for the pharmaceutical agent being most accumulated in the brain of the fish.

The accuracy of the longitudinal diffusion term (b-term) plays a vital role in the study of mass transfer mechanisms in high performance liquid chromatography (HPLC). In this study, three commonly used methodologies (peak parking; fitting of an experimental van Deemter curve; and the so-called dynamic method) for the determination of the b-term constant were investigated in detail. The three methods were compared based on their mutual agreement, the intra- and inter-day variation of the obtained values and the time required to measure them. Whereas the dynamic method was found to be plagued by impractically long waiting times and concomitant baseline variations compromising accurate measurements of the band broadening, the two other methods lead to very similar b-values, i.e., well within the 1% RSD inter-day variation typically marking both methods in the present study. The best way to study the agreement of the peak parking and plate height fitting method is in a plot of h.ν versus ν, providing a much better zoom on the b-term region of the van Deemter curve than the customarily employed h versus ν-curve and hence allowing to identify any anomalous measurement values (usually related to measurements with a long experimentation time). Verifying the mutual agreement between both methods is proposed here as an additional accuracy check of the obtained data.

In this paper, the degradation of sulfamethoxazole (SMX) was investigated using the ferrous iron (Fe2+) activation of persulfate (PS) (the Fe2+/PS process). The influence of the initial concentration of both PS and Fe2+ was investigated. It was found that increasing the PS concentration resulted in a higher SMX degradation efficiency. The influence of inhibiting reactions was found to increase with increasing Fe2+ concentration. In order to minimize these inhibiting reactions, different dosing strategies were applied. It was found that the SMX degradation efficiency could be enhanced significantly when changing from direct dosing (total amount of Fe2+ dosed at the start) to sequential dosing (dosing that same total amount but divided over specific time intervals) and even more when using continuous dosing (dosing the same total amount but continuously over 30 min reaction time). The contribution of different reactive species in this process was also investigated. It was found that hydroxyl radicals (•OH) were mainly responsible for the degradation of SMX during direct dosing, while using continuous dosing of Fe2+, the contribution of Fe(IV) and sulfate radicals (•SO4-) became more important (reduction of •OH contribution from 89 to 71%). Some degradation products formed during the SMX degradation process were identified and the difference in reaction mechanism between •OH on the one hand and Fe(IV) and •SO4- on the other hand was elucidated. At last, a comparison of different sulfate radical based advanced oxidation processes (SR-AOP) is performed by comparing the difference in SMX degradation efficiency, reactive species contribution and the formed degradation products. In most investigated processes, similar degradation products have been found, however, the large •OH contribution in the Fe2+/PS process resulted in distinct degradation products.

The use of heat-activated peroxymonosulfate oxidation for the degradation of the antibiotic compound sulfamethoxazole (SMX) was studied in this paper. It was found that the degradation process follows a pseudo-first order kinetic model. Increasing the oxidant concentration and/or the activation temperature led to a higher sulfamethoxazole degradation efficiency. Increasing the pH from 3 to 9.5 resulted in a higher degradation efficiency as well, although the SMX degradation was significantly inhibited at a pH of 11. Through radical scavenging experiments, it was found that both •OH and •SO4− played a role in the SMX degradation mechanism. Seven transformation products were identified in the SMX degradation process. Both the radicals present and the initial pH value of the degradation process were found to influence the formation of several degradation products. Finally, the heat-activated peroxymonosulfate oxidation process was compared with the heat-activated persulfate process and the main intermediates formed in both processes were identified and compared with each other.

A frequently encountered problem in the practical application of nano- and microflow hydrophilic interaction chromatography (HILIC) columns is the distortion of peak shapes arising from a mismatch between the sample solvent and the mobile phase. An unmatched or improperly matched sample solvent can distort the peak shape of analytes and influence their retention times, thereby affecting the quality of the resulting chromatogram. In this work, the effect of sample solvent composition (mixtures of acetonitrile, water, methanol and isopropanol in different ratios) and injection volume (20–100 nL) was systematically investigated using a selection of neutral and charged compounds on a series of zwitterionic and charged small I.D. (0.1–0.3 mm) HILIC columns. For retained compounds, pure ACN was demonstrated to be the best sample solvent to obtain narrow peaks, while for compounds that eluted very close to the solvent peak, the peak shape was distorted when the sample solvent consisted of pure ACN. A highly aqueous sample solvent, which interferes with the partitioning of polar analytes into the stationary phase, was demonstrated to be detrimental for the peak shape of retained neutral compounds, while for unretained compounds that do not or hardly interact with the stationary phase, a high amount of water in the sample solvent was not problematic. For charged compounds, water in the sample solvent favored the electrostatic attraction with the stationary phase. Therefore, the retention time of charged analytes was shown to increase with increasing water content in the sample solvent. Even when a large amount of water was present in the sample solvent, the peak shapes of these compounds were still acceptable. For highly polar compounds with a limited solubility in aqueous sample solvents, it was found that a mixture of ACN and MeOH or IPA is a good alternative.

This study explores the efficiency and kinetics of the photoactivated periodate process for the degradation of 2,4-dichlorophenol (2,4-DCP) in water. The obtained results show that the degradation rate was considerably higher for UV/IO4- compared to UV irradiation alone. Pseudo first-order reaction rate kinetics were obtained for all process conditions. The pH did not have a significant impact on the decomposition of 2,4-DCP using photoactivated periodate. Therefore, the applied method can be used to treat (waste)water at various pH. By raising the initial concentration of periodate to 5 mM, the degradation rate increased, while it decreased again at a concentration of 8 mM. As the 2,4-DCP concentration increased, the removal rate decreased. The extent of degradation was observed to be proportional with the UV intensity. A mechanistic study revealed that iodine radicals dominated the degradation of 2,4-DCP by photoactivated periodate, whereas OH and O(3P) only played a minor role. At pH 5.0, all chlorine atoms in 2,4-DCP were released as chloride ions in the UV/IO4- process, hence reaching a total dechlorination. Finally, the presence of inorganic salts, even at high levels, did not significantly impact the degradation. According to the results achieved in this study, the UV/IO4- system can be considered as a valuable alternative to treat effluents containing chlorinated organic compounds such as pulp and paper mill effluents and brine (waste)water.

An analytical procedure to measure the whole-body uptake of pharmaceuticals in zebrafish has been developed using state-of-the-art methodologies. A sample preparation procedure for 9 pharmaceuticals displaying a variety in physicochemical properties was developed using 10-day old zebrafish (TG898). For an efficient homogenization of the samples and subsequent recovery of the compounds of interest, different amounts of organic solvents in combination with acidic modifiers were added to zebrafish samples. Samples were subsequently processed using a powerful bath sonicator and centrifuged. Supernatant was then removed and evaporated in a vacuum oven before being reconstituted in a mobile phase-like solvent. Samples were analyzed using ultra-high performance liquid chromatography (UHPLC) on an Acquity BEH C18 column (100 × 2.1mm, dp=1.7µm) coupled to a Waters Xevo TQ-S mass spectrometer. For this purpose, a generic gradient was run, wherein the percentage of acetonitrile was varied from 3% to 82% in 10.5min at a flow rate of 0.41mL/min. Linearity of the method was demonstrated for all compounds (R2 > 0.997) in a practically relevant concentration range. Matrix effects were between 81% and 106%, except for amitriptyline (51%). Using this method, it was demonstrated that a sample pretreatment using 1:2 (v/v) water:methanol in combination with 0.1% formic acid resulted in acceptable recoveries between 74% and 100% for all compounds. Together with the obtained lower limits of quantification of the analytical method (between 0.005 and 1.5ng/mL), this allowed the use of a single zebrafish to study the whole-body uptake of a particular drug, after incubating zebrafish at the maximum tolerated concentration for this drug.