Consumers' Perception of Generic Medicines and Evaluation of In Vitro Quality Control Parameters of Locally Manufactured Paracetamol Tablets in Asmara, Eritrea: A Cross-Sectional Study.

Generic medicines are clinically equivalent and can be used interchangeably for their intended use. Globally, the usage of generic medicines is highly recommended because of their affordability and accessibility. However, consumers hold a negative perception and attitude of using generic medicine as they consider it poor and having inferior quality compared to branded medicines. This study was conducted to assess the consumers' general view of generic medicines and in vitro evaluation of a locally produced generic medicine, paracetamol. An analytical and cross-sectional study was conducted in three selected hospitals, and in vitro quality control evaluation was done in National Drug Quality Control Laboratory between October 26 and November 21, 2017, in Asmara, Eritrea. A systematic random sampling design was employed, and the data was collected using a questionnaire and a check-list for recording the quality control parameters of paracetamol tablets. A total of 403 respondents were included in the study. The majority of the study participants were females (61.8%). Generally, about half (49.1%) of the respondents choose locally manufactured paracetamol over the imported ones. More than half (68.5%) of the respondents did not believe expensive medicines are of better quality. The main reason consumers prefer the local paracetamol (Azemol) tablet to the imported one was due to their good experience (62.1%). About three-fourths (78.1%) of the consumers also believed that medicines manufactured abroad confer higher quality. At the multivariate level, having educational backgrounds such as elementary (AOR = 4.19, 95% CI: 1.251, 14.035) and junior (AOR = 2.4, 95% CI: 1.146, 5.028) was associated with preferability to local paracetamol as a pain killer over the brand ones. The in vitro test of the local paracetamol met the standard specification for the identification test, weight variation test, pharmacopeial test, friability test, disintegration test, and dissolution test. In conclusion, the majority of the consumers considered local paracetamol as having an inferior quality when compared with brand paracetamol. However, the reality revealed that the local paracetamol was of the same quality as the brand ones. To facilitate widespread use of generic medicines, healthcare professionals should educate consumers on the advantages of these medicines.

Effect of Pseudomonas moorei KB4 Cells' Immobilisation on Their Degradation Potential and Tolerance towards Paracetamol.

Pseudomonas moorei KB4 is capable of degrading paracetamol, but high concentrations of this drug may cause an accumulation of toxic metabolites. It is known that immobilisation can have a protective effect on bacterial cells; therefore, the toxicity and degradation rate of paracetamol by the immobilised strain KB4 were assessed. Strain KB4 was immobilised on a plant sponge. A toxicity assessment was performed by measuring the concentration of ATP using the colony-forming unit (CFU) method. The kinetic parameters of paracetamol degradation were estimated using the Hill equation. Toxicity analysis showed a protective effect of the carrier at low concentrations of paracetamol. Moreover, a pronounced phenomenon of hormesis was observed in the immobilised systems. The obtained kinetic parameters and the course of the kinetic curves clearly indicate a decrease in the degradation activity of cells after their immobilisation. There was a delay in degradation in the systems with free cells without glucose and immobilised cells with glucose. However, it was demonstrated that the immobilised systems can degrade at least ten succeeding cycles of 20 mg/L paracetamol degradation. The obtained results indicate that the immobilised strain may become a useful tool in the process of paracetamol degradation.

Innovative spherical biochar for pharmaceutical removal from water: Insight into adsorption mechanism.

In this study, we developed an innovative spherical biochar with high porosity and excellent paracetamol (PRC) adsorption capacity. The optimal pyrolysis temperatures for the preparation of spherical biochar (derived from pure glucose) and non-spherical biochar (from pomelo peel wastes) were obtained at 900 °C and 700 °C, respectively. Various advanced techniques were applied to characterize the prepared biochars. Spherical and non-spherical biochars exhibited large specific surface area (1292 and 1033 m2/g) and high total pore volume (0.704 and 1.074 cm3/g), respectively. The adsorption behavior of PRC onto two biochars was conducted utilizing batch experiments. Results demonstrated that the adsorption process was slightly affected by the change of solution pH (2-11) and addition of NaCl (0.05-1.0 M) and was able to achieve fast equilibrium (∼120 min). The maximum adsorption capacity of spherical biochar (286 mg/g) for PRC was approximately double that of non-spherical biochar (147 mg/g). The signal of thermodynamic parameters was negative ΔG° and ΔH° values, but positive ΔS° value. The adsorption mechanism consisted of pore-filling, hydrogen bonding formations, n-π and π-π interactions, and van der Waals force. The adsorption capacities of two biochars were insignificantly dependent on different real water samples containing PRC. Consequently, the biochars can serve as a green and promising material for efficiently removing PRC from water.

Biocatalytic properties of cell surface display laccase for degradation of emerging contaminant acetaminophen in water reclamation.

The surface display laccase (SDL) biocatalyst, where the enzyme laccase is displayed on the surface of biological cells through synthetic biology, provides a new opportunity to develop sustainable technologies for removal of emerging contaminants from wastewater. This study vigorously characterized biocatalytic properties of the SDL in comparison to free laccase in removing emerging contaminant acetaminophen (APAP), with the aim to understand the effect of surface display on enzyme functionality and identify the strategy to overcome the potential limitation. The SDL could effectively remove APAP. Adding redox mediators substantially improved the removal efficiency. The Michaelis-Menten kinetic analysis showed that the redox mediator 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonate could overcome the limitation of APAP accessing the active site of laccase in the SDL biocatalyst. The APAP removal rate catalyzed by the SDL in real secondary wastewater effluent was higher than that in acetate buffer; comprehensive enzyme kinetic analysis provided clear evidence that there were redox mediating compounds in the wastewater. Analysis of transformation products revealed that surface display did not change laccase functionality in terms of APAP transformation mechanism. In addition, the SDL retained 88% of the initial activity after six repeated APAP biotransformation reactions. Results from this study provide a scientific basis for developing and implementing SDL as an innovative biocatalytic material for contaminant treatment applications.

Simultaneous Voltammetric Determination of Acetaminophen, Ascorbic Acid and Uric Acid by Use of Integrated Array of Screen-Printed Electrodes and Chemometric Tools.

In the present work, ternary mixtures of Acetaminophen, Ascorbic acid and Uric acid were resolved using the Electronic tongue (ET) principle and Cyclic voltammetry (CV) technique. The screen-printed integrated electrode array having differentiated response for the three oxidizable compounds was formed by Graphite, Prussian blue (PB), Cobalt (II) phthalocyanine (CoPc) and Copper oxide (II) (CuO) ink-modified carbon electrodes. A set of samples, ranging from 0 to 500 µmol·L-1, was prepared, using a tilted (33) factorial design in order to build the quantitative response model. Subsequently, the model performance was evaluated with an external subset of samples defined randomly along the experimental domain. Partial Least Squares Regression (PLS) was employed to construct the quantitative model. Finally, the model successfully predicted the concentration of the three compounds with a normalized root mean square error (NRMSE) of 1.00 and 0.99 for the training and test subsets, respectively, and R2 ≥ 0.762 for the obtained vs. expected comparison graphs. In this way, a screen-printed integrated electrode platform can be successfully used for voltammetric ET applications.

Efficacy of removal of a popular NSAID from aqueous solutions with metalloligs.

Acetaminophen, a popular NSAID (Non-steroidal anti-inflammatory drug), was studied for efficacy of removal from aqueous solutions. While Octolig® (a polyethylenediimine covalently attached to silica gel) is able to remove many simple anions and some acidic pharmaceuticals having a pKa value less than 4.5, it lacked efficacy with acetaminophen. Accordingly different transition- metal derivatives of Octolig® were tested by column chromatography using as substrates Octolig® derivatives of copper(II), cobalt(II), iron(III), manganese(II), nickel(II), and zinc(II).

An electrochemical sensor based on electro-polymerization of caffeic acid and Zn/Ni-ZIF-8-800 on glassy carbon electrode for the sensitive detection of acetaminophen.

A new electrochemical sensor was fabricated for the sensitive and selective detection of acetaminophen (AP), based on a bare glassy carbon electrode (GCE) modified with poly caffeic acid (PCA) and Zn/Ni-ZIF-8-800 using an electro-polymerization method. The carbon material of Zn/Ni-ZIF-8-800 derived from bimetal-organic framework was synthesized by one-step pyrolysis method. Then, the as-prepared materials and the corresponding fabricated sensors were fully characterized by XRD, FTIR, BET, SEM, TEM and XPS analyses. In addition, the electron transfer abilities of the modified sensors were investigated by CV and EIS. Subsequently, the parameters of polymerization time, pH value and scan rate were systematically studied and optimized. Under the optimum conditions, the desirable linear relationships were obtained between the peak current and the AP concentration at the PCA@ Zn/Ni-ZIF-8-800/GCE sensor with a detection limit of 0.0291 µM. The outstanding electrochemical performance of the proposed sensor can be attributed to the good electrocatalytic activity of PCA, the large surface area and high conductivity of Zn/Ni-ZIF-8-800 as well as the synergistic effect of PCA and Zn/Ni-ZIF-8-800. Moreover, the fabricated sensor was also successfully applied for the determination of AP in pharmaceutical dosage forms and human urine sample, and satisfactory recoveries were obtained.

Multi-Spheres Adsorptive Microextraction (MSAµE)-Application of a Novel Analytical Approach for Monitoring Chemical Anthropogenic Markers in Environmental Water Matrices.

Multi-spheres adsorptive microextraction using powdered activated carbons (ACs) was studied as a novel enrichment approach, followed by liquid desorption and high-performance liquid chromatography with diode array detection (MSAµE(AC)-LD/HPLC-DAD) to monitor caffeine (CAF) and acetaminophen (ACF) traces in environmental matrices. In this study, commercial activated carbons (N, NOX, and R) were tested, with the latter showing a much better performance for the analysis of both anthropogenic drugs. The main parameters affecting the efficiency of the proposed methodology are fully discussed using commercial AC(R). Textural and surface chemistry properties of the ACs sample were correlated with the analytical results. Assays performed on 30 mL of water samples spiked at 10 µg L-1 under optimized experimental conditions, yielding recoveries of 75.3% for ACF and 82.6% for CAF. The methodology also showed excellent linear dynamic ranges for both drugs with determination coefficients higher than 0.9976, limits of detection and quantification of 0.8⁻1.2 µg L-1 and 2.8⁻4.0 µg L-1, respectively, and suitable precision (RSD < 13.8%). By using the standard addition method, the application of the present method to environmental matrices, including superficial, sea, and wastewater samples, allowed very good performance at the trace level. The proposed methodology proved to be a feasible alternative for polar compound analysis, showing to be easy to implement, reliable, and sensitive, with the possibility to reuse and store the analytical devices loaded with the target compounds for later analysis.

Simultaneous voltammetric determination of acetaminophen and isoniazid using MXene modified screen-printed electrode.

Determination of hepatotoxic drugs is critical for both clinical diagnosis and quantity control of their pharmaceutical formulations. In this work, a facile and sensitive sensor based on MXene modified screen-printed electrode (MXene/SPE) has been developed for detection of acetaminophen (ACOP) and isoniazid (INZ), which are two commonly used drugs but might induce liver damage in certain circumstances. MXene showed excellent electrocatalytic activity toward the oxidation of ACOP and INZ compared with bare SPE in 0.1 M H2SO4, and the separated oxidation peak potentials ensured simultaneous detection of the targets with wide linear ranges from 0.25 to 2000 µM for ACOP and 0.1-4.6 mM for INZ. The detection limits of ACOP and INZ were 0.048 µM and 0.064 mM, respectively. (S/N = 3). MXene/SPE exhibits good stability, reproducibility and repeatability, and the method has been successfully applied for detection of ACOP and INZ in their pharmaceutical and biological samples with satisfactory recovery.

Comparison of the paracetamol electrochemical determination using boron-doped diamond electrode and boron-doped carbon nanowalls.

Two different type of electrodes, boron-doped diamond electrode (BDD) and boron-doped carbon nanowalls (B:CNW) electrode, were used for the electrochemical determination of paracetamol using the cyclic voltammetry and the differential pulse voltammetry in phosphate buffered saline, pH = 7.0. The main advantage of these electrodes is their utilization without any additional modification of the electrode surface. The peak current was linearly related to the concentration of paracetamol in the range from 0.065 µM to 32 µM for BDD electrode and from 0.032 µM to 32 µM for B:CNW electrode. The limit of detection was 0.430 µM and 0.281 µM for BDD and B:CNW electrode, respectively. Additionally, we studied the effect of pH on the redox reaction of paracetamol at the both electrodes in Britton-Robinson buffer solution in the range of pH 3.0-12.0, indicating the pH 7.0 value as the most suitable for the current experiments. The studies also included the various scan rates in range of 50-500 mV/s. Finally, our team selected the B:CNW electrode for the determination of paracetamol in the artificial urine sample using differential pulse voltammetry method, obtaining the calculated limit of detection on the level of 0.08006 µM.

Visible-light activation of TiO2 by dye-sensitization for degradation of pharmaceutical compounds.

This work reports the improvement in the photon absorption and degradation of acetaminophen (ACF) and diclofenac (DFC) by photosensitizing TiO2 with two types of dyes Eosin Y (Ey) and Rhodamine B (RhB). Experimental tests were carried out in a solar simulator for three hours for different systems and both pollutants. The influences of the TiO2 concentration (100, 200 and 800 mg L-1) and the catalyst-dye ratio (2%, 5% and 10%) were investigated. The degradation of the compounds was higher in the presence of TiO2-Ey compared to the TiO2-RhB and TiO2 for both pharmaceutical compounds, which was attributed to the anionic nature of Ey. DFC total degradation was achieved using 100 mg L-1 of catalyst loading and 10% of catalyst-dye ratio and the highest ACF degradation (71%) was obtained at 800 mg L-1 of catalyst loading and 5% of catalyst-dye ratio. The photon absorption was studied for both dyes using the six-flux absorption scattering model (SFM) for estimating the LVRPA (local volumetric rate of photon absorption). This was done by modifying the apparent optical thickness equation. It was found that the presence of dye in the photocatalytic systems considerably increases the LVRPA. The rate coefficients for the degradation of pharmaceutical compounds in the presence of the organic dyes were also obtained.

Physical-chemical interactions between pharmaceuticals and biochar in synthetic and real urine.

This research advances the knowledge of the pharmaceutical removal interactions by biochar in synthetic and real urine through the use of reference adsorbents and adsorbate probes. Earlier work has combined biochar and urine for pharmaceutical removal, however, the interactions that influence adsorption are unknown. In this study, bamboo biochar and softwood biochar were chosen as the representative materials and the model pharmaceuticals were naproxen and paracetamol. To further investigate the physical-chemical interactions, two nonpolar adsorbates, para-xylene and dimethylnaphthalene, were tested. Graphite and anion exchange resin, were used to isolate van der Waals and electrostatic interactions, respectively. Experimental kinetic and equilibrium data were fit to multiple adsorption models where the pseudo-second order and Freundlich exhibited the best fit, respectively. The Freundlich and Langmuir parameters had similar trends showing that softwood had the highest adsorption capacity. The model parameters indicated higher selectivity for nonpolar para-xylene and dimethylnaphthalene by graphite and polar paracetamol and naproxen by softwood biochar. The decreasing trend of importance of key interactions for pharmaceutical sorption to biochar are: van der Waals > hydrogen bonding > electrostatic interactions. No statistically significant difference was found between urine age (fresh vs. hydrolyzed) and pharmaceutical removal; however, the urine matrix (synthetic vs. synthetic with metabolites vs. real urine) did show a statistically significant difference on pharmaceutical removal where synthetic urine had comparatively greater adsorption. As constituents (i.e., metabolites) were added to urine matrices, reduced adsorption of pharmaceuticals was observed, indicating that adsorption processes should be tested in real urine for accuracy.

Determination of synthetic pharmaceutical adulterants in herbal weight gain supplements sold in herb shops, Tehran, Iran.

BACKGROUND: Nowadays with the growing popularity of herbal remedies across the world, large sections of population rely on herbal drug practitioners for their primary care. Therefore there is a need to ensure about the safety of herbal drugs and to detect adulteration with undeclared active pharmaceutical ingredients. Herbal drugs are used as first-line drug therapy in some instances. Unfortunately even if there are claims as to be natural, undeclared active pharmaceutical ingredients have been detected in these supplements. OBJECTIVES: The purpose of the present study was to analyse herbal weight gain drugs collected from herb shops located in Tehran, Iran to detect hidden pharmaceutical ingredients using UHPLC and GC/MS instrumentations. METHODS: Sixty herbal drugs advertised as weight gain supplements were gathered from herb shops Tehran province, Iran. All samples were analysed from analytical toxicology point of view to detect undeclared active pharmaceutical ingredients. Method was validated for quantitative analysis of cyproheptadine and dexamethasone. RESULTS: Method validity parameters showed good results for quantitative analysis of pharmaceutical ingredients. Cyproheptadine, dexamethasone, sildenafil, tramadol, caffeine and acetaminophen were detected in herbal weight gain drugs. Analysed dosage forms contained cyproheptadine and dexamethasone in concentrations higher than therapeutic doses. Quantitative analysis of contaminated drugs showed that the content of pharmacologic ingredients were 0.2-67 and 5.5-10.1 mg/tablet or capsule for cyproheptadine and dexamethasone respectively. CONCLUSIONS: Despite natural supplements producers' claim, herbal weight gain drugs were not natural at all. Undeclared active pharmaceutical ingredients can predispose patients to health problems and even life-threatening situations. Graphical Abstract ᅟ.

Removal of acetaminophen from synthetic wastewater in a fixed-bed column adsorption using low-cost coconut shell waste pretreated with NaOH, HNO3, ozone, and/or chitosan.

Acetaminophen (Ace) is a trace pollutant widely found in sewage treatment plant (STP) wastewater. We test the feasibility of coconut shell waste, a low cost adsorbent from coconut industry, for removing Ace from synthetic solution in a fixed-bed column adsorption. To enhance its performance, the surface of granular activated carbon (GAC) was pre-treated with NaOH, HNO3, ozone, and/or chitosan respectively. The results show that the chemical modification of the GAC's surface with various chemicals has enhanced its Ace removal during the column operations. Among the modified adsorbents, the ozone-treated GAC stands out for the highest Ace adsorption capacity (38.2 mg/g) under the following conditions: 40 mg/L of Ace concentration, 2 mL/min of flow rate, 45 cm of bed depth. Both the Thomas and the Yoon-Nelson models are applicable to simulate the experimental results of the column operations with their adsorption capacities: ozone-treated GAC (20.88 mg/g) > chitosan-coated GAC (16.67 mg/g) > HNO3-treated GAC (11.09 mg/g) > NaOH-treated GAC (7.57 mg/g) > as-received GAC (2.84 mg/g). This suggests that the ozone-treated GAC is promising and suitable for Ace removal in a fixed-bed reactor.

Cellulose membrane modified with polypyrrole as an extraction device for the determination of emerging contaminants in river water with gas chromatography-mass spectrometry.

In this study, a simple, efficient, and reusable device based on cellulose membranes modified with polypyrrole was developed to extract 14 emerging contaminants from aqueous matrices. For chemical polymerization, a low-cost cellulose membrane was immersed in 0.1 mol/L pyrrole and 0.5 mol/L ammonium persulfate for 40 min in an ice/water bath. The cellulose membranes modified with polypyrrole were accommodated in a polycarbonate holder suitable for solid-phase extraction disks. Solid-phase extraction parameters that affect extraction efficiency, such as sample volume, pH, flow rate, and desorption were optimized. Subsequently, determination of target compounds was performed by gas chromatography with mass spectrometry. The linear range for analytes ranged from 0.05 to 500 µg/L, with coefficients of determination above 0.990. The limits of quantification varied between 0.05 and 10 µg/L, with relative standard deviations lower than 17%. The performance of the proposed cellulose membranes modified with polypyrrole device for real samples was evaluated after extraction of emerging contaminants from a river water sample from the city of Curitiba, Brazil. Bisphenol A (6.39 µg/L), caffeine (17.83 µg/L), and paracetamol (19.28 µg/L) were found in these samples.

Application of as-synthesised MCM-41 and MCM-41 wrapped with reduced graphene oxide/graphene oxide in the remediation of acetaminophen and aspirin from aqueous system.

In this study, ASM41 (as-synthesised MCM-41), MCM-41, MCM-41 encapsulated with graphene oxide (MCM-41-GO) and reduced graphene oxide (MCM-41-G) were fabricated and utilized in the remediation of acetaminophen and aspirin from water. A surfactant template (cetyltrimethylammonium bromide) was added to ASM41 to make it more hydrophobic and its effects on the remediation of acetaminophen and aspirin from wastewater was studied. To further improve the adsorption capacity of the adsorbent, MCM-41 was encapsulated with GO and G which also aided in easy separation of the adsorbent from the aqueous solution. Comparative studies of the adsorption of acetaminophen and aspirin on all four adsorbents were investigated. Batch adsorption studies of acetaminophen and aspirin were carried out to determine the effects of pH, initial concentration, time and adsorbent dose. Adsorption mechanism was through EDA, π-π interactions, and hydrophobic effects. Data from sorption kinetics showed ASM41 had the highest qm value for aspirin (909.1 mg/g) and MCM-41-G had the highest qm value for acetaminophen (555.6 mg/g). The significant adsorption by ASM41 can be attributed to increased hydrophobicity due to the retention of the surfactant template. Thermodynamic studies revealed the adsorption process as spontaneous and exothermic. Desorption studies revealed that adsorbents could be regenerated and reused for adsorption.

Evaluation of the effectiveness and mechanisms of acetaminophen and methylene blue dye adsorption on activated biochar derived from municipal solid wastes.

The adsorption potential and governing mechanisms of emerging contaminants, i.e. acetaminophen or acetyl-para-aminophenol (APAP) and methylene blue (MB) dye, on activated carbon derived from municipal solid waste were investigated in this work. Results showed that MB adsorption was significantly more effective, with a maximum removal of 99.9%, than APAP adsorption (%Rmax = 63.7%). MB adsorption was found to be unaffected by pH change, while the adsorption capacity of APAP drastically dropped by about 89% when the pH was adjusted from pH 2 to 12. Surface reactions during APAP adsorption was dominated by both physical and chemical interactions, with the kinetic data showing good fit in both pseudo-first order (R2 = 0.986-0.997) and pseudo-second order (R2>0.998) models. On the other hand, MB adsorption was best described by the pseudo-second order model, with R2>0.981, denoting that chemisorption controlled the process. Electrostatic attractions and chemical reactions with oxygenated surface functional groups (i.e., -OH and -COOH) govern the adsorption of APAP and MB on the activated biochar. Thermodynamic study showed that APAP and MB adsorption were endothermic with positive ΔH° values of 16.5 and 74.7 kJ mol-1, respectively. Negative ΔG° values obtained for APAP (-3.7 to -5.1 kJ mol-1) and MB (-11.4 to -17.1 kJ mol-1) implied that the adsorption onto the activated biochar was spontaneous and feasible. Overall, the study demonstrates the effectiveness of activated biochar from municipal solid wastes as alternative adsorbent for the removal of acetaminophen and methylene blue dye from contaminated waters.

Fluorescence turn-off-on probe based on polypyrrole/graphene quantum composites for selective and sensitive detection of paracetamol and ascorbic acid.

In this work, we presented a novel biosensor for rapid detection of paracetamol and ascorbic acid. The novel biosensor was based on the fluorescent "turn off-on" of polypyrrole/graphene quantum dots (PPy/GQDs) composites. The composites exhibit strong fluorescence emission, which is dramatically enhanced as high as three times than that of pure GQDs. It is found that the fluorescence intensity of PPy/GQDs can be efficiently quenched by N-acetyl-p-benzoquinone (4-AOBQ), the oxidation product of paracetamol (PAR). And a turn-on fluorescence signal was observed when 4-AOBQ is reduced by ascorbic acid (AA). The quenched and recovered fluorescence intensity of PPy-GQDs was proportional to the concentration of PAR (0.067-233µg/L) and AA (3.33-997.5µg/L) respectively. The limit of detection is 0.022µg/L for PAR and 1.05µg/L for AA. The present method was applied to the determination of PAR and AA in human serum samples with satisfactory results.

Ozonation as a pretreatment process for nanofiltration brines: Monitoring of transformation products and toxicity evaluation.

Considerable interest has been given to using nanofiltration (NF) in lieu of reverse osmosis for water reclamation schemes due to lower energy consumption, higher flux rates while ensuring good micropollutants rejection. The application NF results in the generation of a large concentrated waste stream. Treatment of the concentrate is a major hurdle for the implementation of membrane technologies since the concentrate is usually unusable due to a large pollutants content. This work focuses on the application of ozonation as pretreatment of urban NF concentrates, the generation of transformation products and their relative toxicity. Three pharmaceutical micropollutants largely encountered in water cycle were selected as target molecules: acetaminophen, carbamazepine and atenolol. Through accurate-mass Q-TOF LC-MS/MS analyses, more than twenty ozonation products were detected, structure proposals and formation pathways were elaborated. Attempts were made to understand the correlation between the transformation products and acute toxicity on Vibrio fischeri strain. It is the first time that an integrated study reported on the ozonation of pharmaceuticals in urban membrane concentrates, in terms of transformation products, kinetics, degradation mechanisms, as well as toxicity assessment.

Remediation of a mixture of analgesics in a stirred-tank photobioreactor using microalgal-bacterial consortium coupled with attempt to valorise the harvested biomass.

An artificial microalgal-bacterial consortium was used to remediate a mixture of analgesics (ketoprofen, paracetamol and aspirin) in a stirred-tank photobioreactor. A hydraulic retention time (HRT) of 3days supported poor treatment because of the formation of p-aminophenol (paracetamol toxic metabolite). Increasing the HRT to 4days enhanced the bioremediation efficiency. After applying an acclimatization regime, 95% removal of the analgesics mixture, p-aminophenol and COD reduction were achieved. However, shortening the HRT again to 3days neither improved the COD reduction nor ketoprofen removal. Applying continuous illumination achieved the best analgesics removal results. The harvested biomass contained 50% protein, which included almost all essential amino acids. The detected fatty acid profile suggested the harvested biomass to be a good biodiesel-producing candidate. The water-extractable fraction possessed the highest phenolic content and antioxidant capacity. These findings suggest the whole process to be an integrated eco-friendly and cost-efficient strategy for remediating pharmaceutical wastewater.