Pharmaceuticals Carbamazepine Research Articles

Priority screening of contaminants of emerging concern (CECs) in surface water: Comparing cell-based bioassays and exposure-activity ratios (EARs)

In this study, we compared a wide range of cell-based bioassays to the use of chemical analysis followed by exposure-activity ratio (EAR) and Toxicological Prioritization index (ToxPi) for prioritizing chemicals, sites, and hazard concerns in water samples. Surface water samples were collected from nine sites in three Central Pennsylvania streams and analyzed for a forty-six contaminants of emerging concern (CECs), including pesticides, personal care products, and pharmaceuticals. Cell-based reporter assays evaluated human and zebrafish molecular initiating events (MIEs) in endocrine and metabolic disruption, altered lipid metabolism, and oxidative stress. Bioassays showed that 12 out of 40 assays had at least one site with activity over the effect-based trigger (EBT) values. The receptors that exhibited the highest number of samples above the EBT that would be expected to cause toxicity were Aryl hydrocarbon receptor (AhR, human and zebrafish), Pregnane X Receptor (PXR), Estrogen Receptor-beta (ERB), and Androgen Receptor (AR). Characterizing the collection sites by their bioactivity aligned closely with the stream in which samples were collected. The sum of all EARs for each chemical indicated that the pharmaceutical Carbamazepine and the pesticides Carbaryl and Atrazine posed the greatest concern. However, predicted activity and site prioritization based on individual chemical analysis and calculated EAR were different than those measured by bioassay, indicating that biologically active chemicals are present in the samples that were not included in the targeted analytes. Taken together, these data show that chemical analysis and EAR analysis are beneficial for prioritization of chemicals, whereas mechanism-based bioassays are more inclusive of known as well as unknown chemical contaminants and thus of more use for overall water quality analysis and site prioritization.

Influence of Temperature on the Toxic Effects of Carbamazepine on the Copepod Tigriopus fulvus: A Transgenerational Full Life Cycle Study

Coastal areas are increasingly exposed to global warming and emerging contaminants from anthropogenic activities; however, the interactive effects of these stress factors in shaping the offspring’s vulnerability to them are poorly understood. The present study aimed to assess the influence of temperature on the toxicity of the pharmaceutical carbamazepine (CBZ) in the parental (F0) and in the first (F1) generation of Tigriopus fulvus, through a full life cycle study, measuring several biological parameters. At control temperature (20 °C), exposure to CBZ significantly inhibited larval development, especially in the F1 generation. In contrast, under warmer conditions (27 °C), even after exposure to CBZ, the development was stimulated, proving that temperature was the main factor influencing it. As regards the other investigated life traits (body length, sex ratio, and fecundity), both temperature and generation modulated toxic effects of CBZ, which is evidenced by the onset of higher alterations in F1 co-exposed copepods. Our findings suggest that temperature and contaminants could increase the long-term vulnerability to stressors of T. fulvus, potentially affecting the population structure over multiple generations of exposure.

Efficient Removing of Pharmaceutical Contaminants of Commercial Carbamazepine by Natural Pyrite‐Induced Fenton Reaction in a Wide pH Range

Pharmaceutical contaminants are causing great attention for the public people, urgently requiring to be eliminated from the environment. Herein, commercial pharmaceutical carbamazepine was chosen as a model to be degraded by a heterogeneous Fenton system using natural pyrite as catalyst. The catalyst was characterized by X‐ray diffraction apparatus, high‐resolution transmission electron microscopy, and X‐ray photoelectron spectroscopy. The elements composition and chemical states of pyrite changed significantly after the Fenton reaction, which promoted the production of active species in the electron transfer process. The degradation efficiency of carbamazepine (2.5 mg/L) can reach 99.71% after 30 min with 0.3 g/L of pyrite and 5 mM of H2O2, respectively. The reaction system was suitable for a wide range of pH (3–9). The environmental adaptability examination of pyrite showed that humic acid (HA) had inhibitory effects on the degradation of carbamazepine. While the changes of degradation efficiency of carbamazepine were inconspicuous in the presence of and , indicating strong anti‐interference to environment common anions. Free‐radical capturers suggested that hydroxyl radical (∙OH), superoxide radical (), and singlet oxygen (1O2) participated in the degradation of carbamazepine. This research has offered a new strategy of “treating wastes with wastes” to use pyrite to remove emerging pollutants.

Mixture effects of pharmaceuticals carbamazepine, diclofenac and venlafaxine on Mytilus galloprovincialis mussel probed by metabolomics and proteogenomics combined approach

Exposure to single molecules under laboratory conditions has led to a better understanding of the mechanisms of action (MeOAs) and effects of pharmaceutical active compounds (PhACs) on non-target organisms. However, not taking the co-occurrence of contaminants in the environment and their possible interactions into account may lead to underestimation of their impacts. In this study, we combined untargeted metabolomics and proteogenomics approaches to assess the mixture effects of diclofenac, carbamazepine and venlafaxine on marine mussels (Mytilus galloprovincialis). Our multi-omics approach and data fusion strategy highlighted how such xenobiotic cocktails induce important cellular changes that can be harmful to marine bivalves. This response is mainly characterized by energy metabolism disruption, fatty acid degradation, protein synthesis and degradation, and the induction of endoplasmic reticulum stress and oxidative stress. The known MeOAs and molecular signatures of PhACs were taken into consideration to gain insight into the mixture effects, thereby revealing a potential additive effect. Multi-omics approaches on mussels as sentinels offer a comprehensive overview of molecular and cellular responses triggered by exposure to contaminant mixtures, even at environmental concentrations.

Chemicals of emerging concern in coastal aquifers: Assessment along the land-ocean interface

Submarine Groundwater Discharge (SGD) is recognized as a relevant source of pollutants to the sea, but little is known about its relevance as a source of chemicals of emerging concern (CECs). Here, both the presence and distribution of a wide range of CECs have been evaluated in the most comprehensive manner to date, in a well-characterized Mediterranean coastal aquifer near Barcelona (Spain). Samples from coastal groundwater and seawater allowed for the unique spatial characterization of the pollutants present in the land-ocean interface, an outstanding research gap that required attention. The main goals were (1) to determine CECs in the aquifer, so as to evaluate the SGD as a relevant source of marine pollution, and (2) to identify new tracers to improve our understanding of SGD dynamics. To this end, 92 CECs were located in the aquifer by using wide-scope analytical target methodologies (>2000 chemicals). Among them, the perfluoroalkyl and polyfluoroalkyl substances (PFAS), along with the pharmaceuticals carbamazepine and topiramate, were revealed to be good markers for tracing anthropogenic contamination in ground- and seawater, in concrete situations (e.g., highly contaminated sites). Additionally, non-target analysis expanded the number of potential tracers, making it a promising tool for identifying both the source and the fate of pollutants.

ORGANICS: A QGIS Plugin for Simulating One-Dimensional Transport of Dissolved Substances in Surface Water

Surface water in streams and rivers is a valuable resource and pollution events, if not tackled in time, may have dramatic impacts on aquatic ecosystems. As such, in order to prepare pollution prevention plans and measures or to set-up timely remedial options, especially in the early stages of pollution incidents, simulation tools are of great help for authorities, with specific reference to environmental protection agencies and river basin authorities. In this paper, we present the development and testing of the ORGANICS plugin embedded in QGIS. The plugin is a first attempt to embed surface water solute transport modelling into GIS for the simulation of the concentration of a dissolved substance (for example an organic compound) in surface water bodies including advection dispersion and degradation. This tool is based on the analytical solution of the popular advection/dispersion equation describing the transport of contaminants in surface water. By providing as input data the concentration measured at the entry point of a watercourse (inlet boundary condition) and the average speed of the surface water, the model simulates the concentration of a substance at a certain distance from the entry point, along the profile of the watercourse. The tool is first tested on a synthetic case. Then data on the concentration of the pharmaceutical carbamazepine monitored at the inlet and outlet of a vegetated channel, in a single day, are used to validate the tool in a real environment. The ORGANICS plugin aims at popularizing the use of simple modelling tools within a GIS framework, and it provides GIS experts with the ability to perform approximate, but fast, simulations of the evolution of pollutants concentration in surface water bodies.

Low-Frequency Vibrational Spectroscopy Characteristic of Pharmaceutical Carbamazepine Co-Crystals with Nicotinamide and Saccharin.

The pharmaceutical co-crystal has attracted increasing interest due to the improvement of physicochemical properties of active pharmaceutical ingredients. The characterization of pharmaceutical co-crystal is an integral part of the pharmaceutical field. In this paper, the low-frequency vibrational properties for carbamazepine co-crystals with nicotinamide and saccharin (CBZ-NIC and CBZ-SAC) have been characterized by combining the THz spectroscopy with low-wavenumber Raman spectroscopy. The experiment results show that, compared with the individual constituents, CBZ-NIC and CBZ-SAC co-crystals not only have different characteristic absorption peaks in the 0.3-2.5 THz region, but also have significant low-wavenumber Raman characteristic peaks in 0–100 cm−1. Density functional theory was performed to simulate the terahertz and low-wavenumber Raman spectra of the two co-crystals, where the calculation agreed well with the measured vibrational peak positions. The vibrational modes of CBZ-NIC and CBZ-SAC co-crystals were assigned through comparing theoretical results with the experimental spectra. Meanwhile, the low-frequency infrared and/or Raman active of characteristic peaks for such co-crystals were discussed. The results indicate the combination of THz spectroscopy and low-wavenumber Raman spectroscopy can provide more comprehensive low-frequency vibrational information for pharmaceutical co-crystals, such as collective vibration and skeleton vibration, which could play an important role in pharmaceutical science.

Marine heatwaves hamper neuro-immune and oxidative tolerance toward carbamazepine in Mytilus galloprovincialis

The increased frequency and intensity of short-term extreme warming phenomena have been associated to harsh biological and ecosystem outcomes (i.e., mass mortalities in marine organisms). Marine heatwaves (MHWs), occurring when seasonal temperature threshold is exceeded for at least 5 consecutive days, may reduce the tolerance of coastal species toward additional pressures, but interactions between such multiple stressors are virtually unexplored. The present study aimed to characterize in Mytilus galloprovincialis the influence of a simulated MHW scenario on the toxicological effects of the pharmaceutical carbamazepine (CBZ), ubiquitously detected in the marine environment and chosen as model compound for this relevant class of emerging contaminants. The bioaccumulation of CBZ and responsiveness of various biological parameters, including immune system, antioxidant status, lipid metabolism and cellular integrity, were analyzed in exposed mussels both during and after the end of the heatwave. MHW appeared to strongly modulate accumulation of CBZ, paralleled by weakened immunocompetence and onset of oxidative disturbance that finally evolved to cellular damages and lipid metabolism disorders. Elaboration of the overall results through a quantitative Weight of Evidence model, revealed the highest hazard in organisms exposed to both the stressors 10 days after the end of the heatwave, suggesting that MHWs could leave a footprint on the capability of mussels to counteract CBZ toxicity, thus affecting their vulnerability and predisposition to adverse effects toward multiple stressors.

Electrochemical Oxidation of Different Therapeutic Classes of Pharmaceuticals Using Graphite-PVC Composite Electrode.

This study reports electrochemical treatment of different therapeutic classes of pharmaceuticals (caffeine, prazosin, enalapril, carbamazepine, nifedipine, levonorgestrel, and simvastatin) in a mixture. The electrochemical process was investigated using graphite-PVC anode at different applied voltages (3, 5, and 12 V), initial concentrations of studied pharmaceuticals in aqueous solution (5 and 10 mg/L), and concentrations of sodium chloride (1 and 2 g/L). The % removal of pharmaceuticals increased with the applied voltage, and was found higher than 98% after 50 min of electrolysis at 5 V. Energy consumption ranged between 0.760 and 3.300 Wh/mg using 12 V being the highest value compared to 3 and 5 V. The formation of chlorinated by-products from four selected pharmaceuticals, simvastatin (C11H13Cl3O5, and C10H12Cl4O3), prazosin (C13H12Cl3N5O3 and C10H11Cl4N2O2), carbamazepine and caffeine (C15H11N2O2Cl and C8H9N4O2Cl) was identified and elucidated using liquid chromatography-time of flight mass spectrometry (LC-TOF/MS).

Occurrence and fate of pharmaceuticals in a wastewater treatment plant from southeast of Spain and risk assessment

Pharmaceutical and personal care products (PPCPs) can be incorporated into ecosystems and pose potential environmental and health hazards. These pollutants are becoming omnipresent in the environment because they are introduced by several sources, being particularly important the contribution of human-derived pharmaceuticals. The presence of PPCPs in waters has received increasing attention in recent years, resulting in great concern regarding their occurrence, transformation, fate and environmental risk. For that reason, the pharmaceuticals carbamazepine (CBZ), diclofenac (DIC), ibuprofen (IBU), ketoprofen (KET) and naproxen (NPX) were measured in the waters and sludge of several parts of a double step activated sludge wastewater treatment plant (WWTP) from Murcia (Spain). With these results, the biological degradation constant, the sorption coefficient and the pharmaceutical removal were calculated. Possible risks to humans and ecosystems were also evaluated.These showed good degradation of IBU and NPX (74.4 and 84.9%, respectively), while CBZ didn't display any degradation. DIC was the compound most likely to be sorbed into the sludge (3.09 L kg−1). The PPCPs removal in this double stage WWTP was compared to a previous data obtained in a WWTP of the same region with an activated sludge (single biological batch reactor). The results showed a decrease in the removal of the double stage plant, probably due to the lower hydraulic retention time employed. The study of the human and ecological risk quotients indicates a low risk of the selected pharmaceuticals (RQ < 0.1).

In situ functionalization of a cellulosic-based activated carbon with magnetic iron oxides for the removal of carbamazepine from wastewater.

The main goal of this work was to produce an easily recoverable waste-based magnetic activated carbon (MAC) for an efficient removal of the antiepileptic pharmaceutical carbamazepine (CBZ) from wastewater. For this purpose, the synthesis procedure was optimized and a material (MAC4) providing immediate recuperation from solution, remarkable adsorptive performance and relevant properties (specific surface area of 551m2g-1 and saturation magnetization of 39.84emug-1) was selected for further CBZ kinetic and equilibrium adsorption studies. MAC4 presented fast CBZ adsorption rates and short equilibrium times (< 30-45min) in both ultrapure water and wastewater. Equilibrium studies showed that MAC4 attained maximum adsorption capacities (qm) of 68 ± 4mgg-1 in ultrapure water and 60 ± 3mgg-1 in wastewater, suggesting no significant interference of the aqueous matrix in the adsorption process. Overall, this work provides evidence of potential application of a waste-based MAC in the tertiary treatment of wastewaters. Graphical abstract.

Effect of Biomass and Operating Condition on Biodegradation Capacity of a Mix of Pharmaceuticals (Carbamazepine, Ibuprofen, and Ciprofloxacin) in a Membrane Bioreactor

AbstractThere is no existing applicable law that regulates compounds of emerging concern (CECs), so they remain a global concern because they are easily taken up by organisms. Because of the curren...

Hydrogen-Bonded Tetramers of Carbamazepine

In this study, the pharmaceutical carbamazepine (CBZ) and the related molecule dibenzazepine (DBZ) are prepared on the Au(111) surface and visualized using scanning tunneling microscopy. Monolayers...

Photocatalytic Degradation of Pharmaceuticals Carbamazepine, Diclofenac, and Sulfamethoxazole by Semiconductor and Carbon Materials: A Review.

The presence of pharmaceutical compounds in the environment is a reality that calls for more efficient water treatment technologies. Photocatalysis is a powerful technology available but the high energy costs associated with the use of UV irradiation hinder its large scale implementation. More sustainable and cheaper photocatalytic processes can be achieved by improving the sunlight harvesting and the synthesis of semiconductor/carbon composites has proved to be a promising strategy. Carbamazepine, diclofenac, and sulfamethoxazole were selected as target pharmaceuticals due to their recalcitrant behavior during conventional wastewater treatment and persistence in the environment, as properly reviewed. The literature data on the photocatalytic removal of carbamazepine, diclofenac, and sulfamethoxazole by semiconductor/carbon materials was critically revised to highlight the role of the carbon in the enhanced semiconductor performance under solar irradiation. Generally it was demonstrated that carbon materials induce red-shift absorption and they contribute to more effective charge separation, thus improving the composite photoactivity. Carbon was added as a dopant (C-doping) or as support or doping materials (i.e., nanoporous carbons, carbon nanotubes (CNTs), graphene, and derived materials, carbon quantum dots (CQDs), and biochars) and in the large majority of the cases, TiO2 was the semiconductor tested. The specific role of carbon materials is dependent on their properties but even the more amorphous forms, like nanoporous carbons or biochars, allow to prepare composites with improved properties compared to the bare semiconductor. The self-photocatalytic activity of the carbon materials was also reported and should be further explored. The removal and mineralization rates, as well as degradation pathways and toxicity of the treated solutions were also critically analyzed.

In vitro biotransformation of pharmaceuticals and pesticides by trout liver S9 in the presence and absence of carbamazepine

The aim of the present study was to develop (i) a technique for identifying metabolites of organic contaminants by using an in vitro system of trout S9 and liquid chromatography-high-resolution mass spectrometry-based identification method and (ii) to apply this technique to identify the interactive potential of carbamazepine on the formation rate of other metabolites. The pharmaceuticals carbamazepine and propranolol and the pesticides azoxystrobin, diazinon, and fipronil were selected as test contaminants. As a result, a total of ten metabolites were identified for the five parent substances, six of which were confirmed using reference standards. Metabolic reactions included hydroxylation, epoxidation, S-oxidation, and dealkylation. The metabolic transformation rate ranged from 0.2 to 3.5 pmol/mg protein/min/μmol substrate. In the binary exposure experiment with increasing carbamazepine concentration, the formation rates of diazinon and fipronil metabolites (MDI2 and MFP2, respectively) increased, while formation of metabolites of propranolol and azoxystrobin (MPR1, MPR2, MPR3, and MAZ1) slowed down. Meanwhile, S9 pre-exposed to carbamazepine produced diazoxon, a toxic metabolite of diazinon, and pyrimidinol, a less toxic metabolite, more rapidly. These results suggest that carbamazepine, a perennial environmental pollutant, might modulate the toxicity of other substances such as diazinon but further in vivo studies are needed.

Influence of salinity and pH on bioconcentration of ionizable pharmaceuticals by the gulf killifish, Fundulus grandis

Estuaries routinely receive discharges of contaminants of emerging concern from urban regions. Within these dynamic estuarine systems, salinity and pH can vary across spatial and temporal scales. Our previous research identified bioaccumulation of the calcium channel blocker diltiazem and the antihistamine diphenhydramine in several species of fish residing in multiple urban estuaries along the Gulf of Mexico in Texas, where field-measured observations of diltiazem in fish plasma exceeded human therapeutic plasma doses. However, there remains a limited understanding of pharmaceutical bioaccumulation in estuarine environments. Here, we examined the influence of pH and salinity on bioconcentration of three pharmaceuticals in the Gulf killifish, Fundulus grandis. F. grandis were exposed to low levels of the ionizable pharmaceuticals carbamazepine, diltiazem, and diphenhydramine at two salinities (5 ppt, 20 ppt) and two pH levels (6.7, 8.3). pH influenced bioconcentration of select weak base pharmaceuticals, while salinity did not, suggesting that intestinal uptake via drinking does not appear to be a major exposure route of these pharmaceuticals in killifish. Compared to our previous pH dependent uptake observations with diphenhydramine in the fathead minnow model, killifish apparent volume of distribution values were markedly lower than fatheads, though killifish bioconcentration factors were similar at high pH and four fold higher at low pH than freshwater fish. Advancing an understanding of environmental gradient influences on pharmacokinetics among fish is necessary to improve bioaccumulation assessments and interpretation of toxicological observations for ionizable contaminants.

Waste biomass gasification char derived activated carbon for pharmaceutical carbamazepine removal from water

Carbamazepine (CBM), a widely occurring pharmaceutical, has been removed from water by upgrading a waste biomass char from a 300 MW biomass gasification power station plant operating in Indonesia. The fuel source is the waste residue palm kernel shell (PKS) after the palm oil extraction process constituting over one million tonnes per year. The resulting waste power station biomass char (CPKS) from the power station gasification process has been converted into high quality activated carbon by carbon dioxide activation as a sequestration opportunity, at different temperatures ranging from 700 to 900°C for 1 or 1.5 hours. The highest BET surface area was 711.5 m2/g and this activated carbon was able to adsorb 1.14 mmol/g or 268.7 mg CBM/g. Equilibrium and kinetic studies have been undertaken.

Carbamazepine, triclocarban and triclosan biodegradation and the phylotypes and functional genes associated with xenobiotic degradation in four agricultural soils

Pharmaceuticals and personal care products (PPCPs) are released into the environment due to their poor removal during wastewater treatment. Agricultural soils subject to irrigation with wastewater effluent and biosolids application are possible reservoirs for these chemicals. This study examined the impact of the pharmaceutical carbamazepine (CBZ), and the antimicrobial agents triclocarban (TCC) and triclosan (TCS) on four soil microbial communities using shotgun sequencing (HiSeq Illumina) with the overall aim of determining possible degraders as well as the functional genes related to general xenobiotic degradation. The biodegradation of CBZ and TCC was slow, with ≤50% decrease during the 80-day incubation period. In contrast, TCS biodegradation was rapid, with ~80% removal in 25 days. For each chemical, when all four soils were considered together, between three and ten phylotypes (from multiple phyla) were more abundant in the soil samples compared to the live controls. The genera of a number of previously reported CBZ, TCC or TCS degrading isolates were present; Rhodococcus (CBZ), Streptomyces (CBZ), Pseudomonas (CBZ, TCC, TCS), Sphingomonas (TCC, TCS), Methylobacillus (TCS) and Stenotrophomonas (TCS) were among the most abundant (chemical previously reported to be degraded is shown in parenthesis). From the analysis of xenobiotic degrading pathways, genes from five KEGG (Kyoto Encyclopedia of Genes and Genomes) Orthology pathways were the most dominant, including those associated with aminobenzoate, benzoate (most common), chlorocyclohexane/chlorobenzene, dioxin and nitrotoluene biodegradation. Several phylotypes including Bradyrhizobium, Mycobacterium, Rhodopseudomonas, Pseudomonas, Cupriavidus, and Streptomyces were common genera associated with these pathways. Overall, the data suggest several phylotypes are likely involved in the biodegradation of these PPCPs with Pseudomonas being an important genus.

Removal of micropollutants from urban wastewater using a UASB reactor coupled to a MBR at different organic loading rates

ABSTRACTThis study examines the removal of micropollutants (MPs) in a hybrid process that combines anaerobic and aerobic redox conditions under different Organic Loading Rates (OLRs).A laboratory-scale pilot-plant composed of an Upflow Anaerobic Sludge Blanket reactor (UASB) combined with a membrane bioreactor (MBR) was operated. Six MPs were analyzed: the hormones estrone, 17-α-ethinyl estradiol and 17-β-estradiol, the plasticizer bisphenol A and the pharmaceuticals carbamazepine and diclofenac. In order to study its influence on removal efficiencies, the system was operated at three different OLRs: high (0.67 ± 0.15 kg COD/m3 d), medium (0.37 ± 0.06 kg COD/m3 d) and low (0.11 ± 0.02 kg COD/m3 d).The results demonstrated the synergistic effects due to the double biological treatment, with removal rates above 90% for the hormones and the plasticizer. Pharmaceuticals were the most resistant compounds, being only partially removed in the liquid phase. Removal rates of the MPs were higher at high OLR of the influent.

Degradation and Fate of Pharmaceutically Active Contaminants by Advanced Oxidation Processes

The purpose of this review is to investigate the use of advanced oxidation processes (AOPs) including ozonation, UV photolysis, Fenton-type processes, UV/H2O2, and other photocatalytic processes to degrade persistent pharmaceutically active contaminants in water. The review focuses on four common pharmaceuticals carbamazepine (CBZ), diclofenac (DCF), sulfamethoxazole (SMX), and trimethoprim (TMP) which are used as exemplars. Insights into the removal efficiency of each compound by AOPs under various applied conditions are systematically elucidated. This review also investigates the fate of these pharmaceuticals during treatment by advanced oxidation treatment. The effectiveness of AOP processes for the degradation of pharmaceuticals varies significantly, depending on factors such as the nature of the process itself, operating conditions, and the target compound. Ozone can completely remove all four pharmaceuticals. By contrast, direct UV photolysis was effective for the removal of DCF and SMX, whereas the combination with H2O2 was essential to improve CBZ and TMP removal. In addition, a large number of transformation products were frequently detected during the degradation of the selected pharmaceuticals by AOPs. In addition, it has been confirmed that several transformation products were more resistant toward the applied AOPs than their original parent compounds. A major challenge with the use of AOPs for the degradation of the selected pharmaceutically active contaminants is the formation of by-products that are often more persistent than the original contaminants. Therefore, the existence of transformation products must be essentially investigated after the treatment of target pharmaceutical contaminants by AOPs in order to evaluate the effectiveness of the applied technique.