Molecular separation of ibuprofen and 4-isobutylacetophenone using octanol organic solution by porous polymeric membranes.

Molecular separation of pharmaceutical contaminants from water has been recently of great interest to alleviate their detrimental impacts on environment and human well-being. As the novelty, this investigation aims to develop a mechanistic modeling approach and consequently its related CFD-based simulations to evaluate the molecular separation efficiency of ibuprofen (IP) and its metabolite 4-isobutylacetophenone (4-IBAP) from water inside a porous membrane contactor (PMC). For this purpose, octanol has been applied as an organic phase to extract IP and 4-IBAP from the aqueous solution due to high solubility of solutes in octanol. Finite element (FE) technique is used as a promising tool to simultaneously solve continuity and Navier-Stokes equations and their associated boundary conditions in tube, shell and porous membrane compartments of the PMC. The results demonstrated that the application of PMC and liquid-liquid extraction process can be significantly effective due to separating 51 and 54% of inlet IP and 4-IBAP molecules from aqueous solution, respectively. Moreover, the impact of various operational / functional parameters such as packing density, the number of fibrous membrane, the module length, the membrane porosity / tortuosity, and ultimately the aqueous solution flow rate on the molecular separation efficiency of IP and 4-IBAP is studied in more details.

Extraction of Ibuprofen from Natural Waters Using a Covalent Organic Framework.

Ibuprofen is one of the most widely used pharmaceuticals, and due to its inefficient removal by conventional wastewater treatment, it can be found in natural surface waters at high concentrations. Recently, we demonstrated that the TpBD-(CF3)2 covalent organic framework (COF) can adsorb ibuprofen from ultrapure water with high efficiency. Here, we investigate the performance of the COF for the extraction of ibuprofen from natural water samples from a lake, river, and estuary. In general, the complexity of the natural water matrix induced a reduction in the adsorption efficiency of ibuprofen as compared to ultrapure water. The best performance, with over 70% adsorption efficiency, was found in lake water, the sample which featured the lowest pH. According to the theoretical calculations, ibuprofen more favorably interacts with the COF pores in the protonated form, which could partially account for the enhanced adsorption efficiency found in lake water. In addition, we explored the effect of the presence of competing pharmaceuticals, namely, acetaminophen and phenobarbital, on the ibuprofen adsorption as binary mixtures. Acetaminophen and phenobarbital were adsorbed by TpBD-(CF3)2 with low efficiency and their presence led to an increase in ibuprofen adsorption in the binary mixtures. Overall, this study demonstrates that TpBD-(CF3)2 is an efficient adsorbent for the extraction of ibuprofen from natural waters as well.

Effect of Spathiphyllum blandum on the removal of ibuprofen and conventional pollutants from polluted river water, in fully saturated constructed wetlands at mesocosm level.

In this study, the effect of Spathiphyllum blandum on the removal of ibuprofen (IB) and conventional pollutants such as chemical oxygen demand (COD), total nitrogen (TN), ammonium (NH4 +-N), total phosphorus (TP), and total suspended solids (TSS) is reported; this, through its use as an emergent vegetation in fully saturated (FS) constructed wetlands (CWs) at mesocosm level treating polluted river water. With the exception of TP and COD, it was found that for TN (12%), NH4 +-N (11%), TSS (19%), and IB (23%), the removals in systems with vegetation were superior to systems without vegetation (p < 0.05). These findings demonstrate the importance of the species S. blandum, in particular, for the removal of ibuprofen, which is an anti-inflammatory drug commonly found in effluents of wastewater treatment plants. Thus, the results obtained provide information that can be used for the design of future efficient large-scale systems using a new ornamental species, mainly under tropical climatic conditions.

TiO2 nanoparticles and C-Nanofibers modified magnetic Fe3O4 nanospheres (TiO2@Fe3O4@C-NF): A multifunctional hybrid material for magnetic solid-phase extraction of ibuprofen and photocatalytic degradation of drug molecules and azo dye.

Accurate sensitive analysis of drug ingredient substances in biological, pharmaceutical and environmental samples and removal of drug ingredient substances in environmental samples owngreat importance for sustaining viability. The realization of these processes using a single material offers significant advantages in terms of cost, time and ease of use. In this study, TiO2 nanoparticles and C-Nanofibers modified magnetic Fe3O4 nanospheres (TiO2@Fe3O4@C-NFs) synthesized as a multifunctional material employing a simple hydrothermal synthesis method. This innovative material was exploited in the magnetic solid-phase extraction (MSPE) method for the preconcentration of ibuprofen and photocatalytic degradation of antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), and azo dye. To our knowledge, no studies have been previously conducted using the same material as magnetic solid-phase extraction adsorbent and magnetically separable photocatalyst. The characterization of TiO2@Fe3O4@C-NFs was carried out by XRD, FE-SEM, EDX and Raman techniques. The main analytical parameters affecting MSPE performance of ibuprofen such as pH, sorbent amount eluent type and volume and sample volume were optimized. The optimum values of the method were determined at the following parameters: pH 4.0, adsorbent amount 150 mg and eluent 2 mL of acetone. Ibuprofen analysis after MSPE was carried out using a high-performance liquid chromatography diode array detection system (HPLC-DAD). The photocatalytic degradation efficiencies of TiO2@Fe3O4@C-NF hybrid material for probe-analytes reached 80-100% and the complete degradation attained within the range of 8-125 min under UV irradiation. Simple preparation, practical isolation from solutions, high efficiency, reproducibility, and sustainability are the main advantages of the TiO2@Fe3O4@C-NFs for MSPE and photocatalytic degradation applications.

Preparation of a thiols ß-cyclodextrin/gold nanoparticles-coated open tubular column for capillary electrochromatography enantioseparations.

Inspired by the distinct chemical and physical properties of nanoparticles, here a novel open-tubular capillary electrochromatography column was prepared by electrostatic assembly of poly(diallydimethylammonium chloride) onto the inner surface of a fused-silica capillary, followed by self-adsorption of negatively charged SH-ß-cyclodextrin/gold nanoparticles. The formation of the SH-ß-cyclodextrin/gold nanoparticles coated capillary was confirmed and characterized by scanning electron microscopy and energy dispersive spectrometry. The results of scanning electron microscopy and energy dispersive spectrometry studies indicated that SH-ß-cyclodextrin/gold nanoparticles were successfully coated on the inner wall of the capillary column. The performance of the SH-ß-cyclodextrin/gold nanoparticles coated capillary was validated by the analysis of six pairs of chiral drugs, namely zopiclone, carvedilol, salbutamol, terbutaline sulfate, phenoxybenzamine hydrochloride, and ibuprofen. Satisfactory enantioseparation results were achieved, confirming the use of gold nanoparticles as the support could enhance the phase ratio of the open-tubular capillary column. Additionally, the stability and reproducibility of the SH-ß-cyclodextrin/gold nanoparticles coated capillary column were also investigated. Then, this proposed method was well validated with good linearity (≥0.999), recovery (90.0-93.5%) and repeatability, and was successfully used for enantioseparation of ibuprofen in spiked plasma samples, which indicated the new column's potential usage in biological analysis.

Small-Scale Spherical Granulation Using a Planetary Centrifugal Mixer.

A concise spherical granulation method is required to prepare extemporaneously granules remanufactured from oral dosage forms for administration to individuals who cannot swallow tablets or capsules. In this study, we determined the feasibility of spherical granulation using a planetary centrifugal mixer. A model formulation, 20% ibuprofen (IBP) granules, was prepared using a lactose/cornstarch (7 : 3, w/w) mixture or D-mannitol as diluents, and changes in granule characteristics (mean diameter (d50), distribution range of granule size (span), and yield) were evaluated according to the amount of water added and the granulation time. The amount of water was assessed using the plastic limit value as measured using a digital force gauge. We successfully produced granules, and larger amounts of water and longer granulation times resulted in larger d50 values and smaller span values. The optimal granulation time was 45 s and the optimal water contents were 70 and 67.5% of the plastic limit value for the lactose/cornstarch mixture and D-mannitol, respectively. When compared to commercial 20% IBP granules, powder X-ray diffraction and differential scanning calorimetry analyses showed that the granulation process did not alter the crystallinity of the drug. Thus, this novel granulation method using a planetary centrifugal mixer may be a promising technique for compounding in pharmacies and in pharmaceutical manufacturing.

A novel liquid-liquid-solid microextraction strategy for bio-sample preparation by in situ self-assembly of zeolitic imidazolate framework 8 on hollow fiber membrane.

A novel liquid-liquid-solid membrane microextraction (LLSMME) method which integrates hollow fiber liquid phase microextraction (HF-LPME) and solid phase microextraction (SPME) was developed for bio-sample preparation. The homogeneous zeolitic imidazolate framework 8 mixed matrix membrane (ZIF-8-MMM) was prepared by in situ self-assembly of ZIF-8 on the inner surface of hollow fiber membrane and employed as a flexible LLSMME device. Incorporating the advantages of both HF-LPME and SPME, the as-fabricated ZIF-8-MMM exhibited excellent performance on the extraction and preconcentration of small molecule drugs of different polarity from complex biological matrices. As a case study, ZIF-8-MMM-based LLSMME coupled with UPLC-MS/MS were developed and validated for determination of ibuprofen, simvastatin and ranitidine at trace levels in rat plasma. The method showed good linearity (r2 > 0.99) and repeatability (RSD < 15%), low limits of detection (2-3 ng mL-1) and high relative recoveries (97.42-103.8%). The enrichment factors were between 87.3 and 112.6. Our study provided a promising strategy for developing more efficient, cost-effective and environmentally friendly technique for bio-sample pretreatment.

Hybrid monoliths with metal-organic frameworks in spin columns for extraction of non-steroidal drugs prior to their quantitation by reversed-phase HPLC.

A (glycidyl methacrylate)-co-(ethylene glycol dimethacrylate) polymer (poly(GMA-co-EDMA)) was functionalized with metal-organic frameworks (MOF) and used as a sorbent for solid-phase extraction (SPE). The polymeric sorbent was prepared in-situ by photopolymerization in a previously wall-modified spin column, and then modified with an amino-modified MOF of type NH2-MIL-101(Cr). The sorbents were used for the extraction of nonsteroidal anti-inflammatory drugs (NSAIDs) from human urine samples. The sorbent was compared with the parent monolith and embedded approach, where the MOF particles are admixed in the polymerization mixture before the in-situ polymerization in the modified spin column. SPE is performed by percolating the sample solutions in a centrifuge, which streamlines the SPE steps. The hybrid composites were characterized by scanning electron microscopy and nitrogen intrusion porosimetry. Three NSAIDs (ketoprofen, flurbiprofen, and ibuprofen) were tested. They were eluted from the sorbent with acidified water-acetonitrile mixtures and subsequently analyzed by reversed-phase HPLC with UV detection. The detection limits varied in the range from 0.1 to 7 µg·L-1, and the precisions (relative standard deviation) were <14% in all the cases. The recoveries were between 71.0 and 78.0% in spiked urine samples. Graphical abstractA hybrid monolith modified with amino-modified MOF [named NH2-MIL-101(Cr)] in wall-modified spin columns was prepared. The resulting micro-extraction device was applied to the extraction and preconcentration of non-steroidal anti-inflammatory drugs.

Efficient degradation of refractory organic contaminants by zero-valent copper/hydroxylamine/peroxymonosulfate process.

Degradation of naproxen, bisphenol S and ibuprofen in a hydroxylamine enhanced zero-valent copper (Cu0) catalyzed peroxymonosulfate system was investigated for the first time. We found that hydroxylamine addition accelerated the reduction of Cu2+ to Cu+ as well as the corrosion of Cu0, and environmental friendly gas nitrogen was the main product of hydroxylamine. Additionally, hydroxyl radical and sulfate radical were identified to be the dominant reaction species by competitive experiments. The degradation of naproxen, bisphenol S and ibuprofen kept highly efficient in the pH range of 3.0-7.0 in Cu0/hydroxylamine/peroxymonosulfate process, with their degradation products identified by HPLC-MS, which showed that Cu0/hydroxylamine/peroxymonosulfate system could be an alternative to remove non-steroidal antiinflammatory drugs or plasticizers in wastewater. Furthermore, the effects of Cu0, hydroxylamine and peroxymonosulfate dosage were studied and optimized by a BBD based response surface model. This study provided a method to solve the disadvantages of Cu0/peroxymonosulfate systems, and gave a promising method to enhance the efficiencies of ZVMs activated system such as iron, cobalt and copper.

A nanohybrid composed of polyoxotungstate and graphene oxide for dispersive micro solid-phase extraction of non-steroidal anti-inflammatory drugs prior to their quantitation by HPLC.

A nanohybrid was prepared from polyoxotungstate anion and graphene oxide (POT/GO) and characterized in terms of porosity by applying Fourier transform infrared and transmission electron microscopy. The nanohybrid was applied as a sorbent for the dispersive micro solid-phase extraction of the non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen, diclofenac, and naproxen. Different types of sorbents were compared, and the POT/GO nanohybrid was found to have the best adsorption affinity. The NSAIDs were quantified via HPLC with UV detection. Under the optimum conditions, the limits of detection (at an S/N ratio of 3) range between 0.02-0.03 ng.mL-1, and the linear response ranges extend from 0.08-200 ng.mL-1, respectively. The relative standard deviations (RSDs) for five replicates at three concentration levels (0.1, 5 and 100 ng.mL-1) of NSAIDs ranged from 4.1 to 6.1%. The applicability of the method was confirmed by analyzing spiked real water samples, and satisfactory results were obtained, with recoveries between 95.6 and 99.6%. Graphical abstract Schematic representation of the polyoxotungstate/graphene oxide nanohybrid preparation.

Mechanism of the hybrid ozonation-coagulation (HOC) process: Comparison of preformed Al13 polymer and in situ formed Al species.

Because of the influence of hydrolysed species from Al-based coagulants on coagulation performance, the performance and mechanism of the developed hybrid ozonation-coagulation (HOC) process using AlCl3·6H2O and preformed Al13 as coagulants were investigated in this study, in which ozonation and coagulation occurred simultaneously within a single unit. It was found that the HOC process exhibited higher organic matter removal performance compared with coagulation and the pre-ozonation-coagulation process. It was found that the high ibuprofen (IBP) removal efficiency in the HOC process was mainly attributed to OH oxidation promoted by in situ formed hydrolysed aluminium species from AlCl3·6H2O and preformed Al13. Furthermore, the surface hydroxyl groups were determined to be the active reaction sites for the HOC process. Due to the higher proportion of surface hydroxyl groups for Al13, the HOC process with preformed Al13 as coagulants (Al13-HOC) exhibited a higher removal performance than that with AlCl3·6H2O as the coagulant (AlCl3-HOC). It was revealed that most of the generated O2- in the Al13-HOC was adsorbed on the surface of Al13 at different pH values, while a considerably lower proportion of adsorbed O2- was observed on the surface of in situ formed Al species from AlCl3·6H2O. Nevertheless, low proportions of adsorbed OH were found on the surfaces of both preformed Al13 and in situ formed Al species, indicating that the OH oxidation for the removal of organic pollutants occurred primarily in the aqueous phase.

Chitosan tailor-made membranes as biopolymeric support for electromembrane extraction.

A chitosan membrane composed by 60% (w/w) chitosan and 40% (w/w) Aliquat®336 has been proposed as a new biopolymeric support for electromembrane extraction. The new support has been characterized by Scanning Electron Microscopy, resulting a 30-35 µm thickness. Amoxicillin, nicotinic acid, hippuric acid, salicylic acid, anthranilic acid, ketoprofen, naproxen and ibuprofen have been successfully extracted using the proposed support. Better enrichment factors were obtained for the acidic polar analytes than for the non-steroidal anti-inflammatory compounds (ranging from 118 for hippuric acid and 20 for ibuprofen). Electromembrane extraction was developed applying a DC voltage of 100 V, 1-octanol as supported liquid membrane and 20 min of extraction. The target analytes have also been satisfactorily extracted from human urine samples, providing high extraction efficiencies. The chitosan membrane is presented as a promising alternative for supporting liquid membrane compared to commonly used materials for this purpose.

Determination of Ibuprofen and Phenylephrine in Tablets by High-Performance Thin Layer Chromatography and in Plasma by High-Performance Liquid Chromatography with Diode Array Detection.

Two chromatographic methods (high performance thin layer chromatography (HPTLC) and high performance liquid chromatography-diode array detector (HPLC-DAD)), were addressed for the analysis of a mixture consisted of phenylephrine hydrochloride and ibuprofen in two forms bulk and their combined dosage form. This binary mixture is considered to be a challenging one as the two drugs differ greatly in their chemical and physical properties. Not only this affects their simultaneous analysis, but also hinders their simultaneous extraction from biological fluids as plasma. That is the reason the literature lacks any report for the simultaneous extraction and analysis of these drugs from biological fluids. The concentration ranges of both drugs were 0.1-2.5 µg/spot and 0.1-100 µg/mL by HPTLC and HPLC, respectively. Not only was the HPLC-DAD method applied to the investigated drugs determination in pharmaceutical preparations, but also in spiked human plasma. Extensive study was conducted to optimize their simultaneous extraction from plasma as it was a crucial step for the in vivo analysis. The results obtained by proposed methods and a reference one were statistically comparable by analysis of variance test. No significant difference was recorded between the mean percent levels determined by the proposed methods and the reference one.

Mesoporous silica from batik sludge impregnated with aluminum hydroxide for the removal of bisphenol A and ibuprofen.

The present study reports the removal of Bisphenol A (BPA) and Ibuprofen (IBP) using adsorbents prepared from batik sludge. The calcite sludge-aluminum hydroxide (CAl) adsorbent was prepared by calcination and followed by aluminum hydroxide impregnation. The batik sludge and prepared adsorbents were characterized by FESEM, TGA, XRD, FTIR and BET techniques. The maximum adsorption capacity, adsorption time, different initial solution pH, ionic strength and regeneration study of the adsorbents were also investigated. Furthermore, the sorption behavior of the pollutants were studied by the Langmuir and Freundlich isotherms. The deposition of Al(OH)3 enhanced the BPA and IBP adsorption capacity on the CAl surface. The maximum removal capacity of BPA and Ibuprofen were 83.53 mg g-1 and 34.96 mg g-1 for the CAl adsorbent. In addition, the kinetic data for BPA and IBP were fitted to the pseudo first order, pseudo second order, Elovich, parabolic diffusion and power function equations to understand the sorption behavior. The adsorption behavior of BPA and IBP was mainly chemisorption. This study shows that CAl is a promising adsorbent for the removal of BPA and IBP.

Crossflow electrochemical filtration for elimination of ibuprofen and bisphenol a from pure and competing electrolytic solution conditions.

For the first time, a crossflow electrochemical filtration system containing multiwalled carbon nanotubes (MWNTs) blended with buckypaper as a flat sheet dual membrane electrode was investigated for the removal of two contaminants of emerging concern, Ibuprofen and Bisphenol A. Breakthrough experiments revealed that a crossflow configuration could be highly efficient in eliminating both contaminants at applied DC potentials of 2 and 3 V over an extended period, from pure salt electrolyte as well as from synthetic secondary wastewater effluent. The shear flow provided consistent surface coverage resulting in excellent sorption performance. The long residence time of the two contaminants within the membrane (18.3 s) was sufficient enough to allow for almost complete degradation of phenolic aromatic products and quinoid rings and the resulting formation of aliphatic carboxylic acids, which was more evident at a higher applied potential (3 V). The formation of the non-toxic aliphatic carboxylic acids is a clear indication of the superior electrochemical performance of the crossflow mode over the dead-end flow-through system. Moreover, this study provides an in-depth understanding of different factors such as filter surface area and residence time that can greatly affect the removal of the contaminants considered.

Adsorption and photocatalytic removal of Ibuprofen by activated carbon impregnated with TiO2 by UV-Vis monitoring.

The removal of Ibuprofen was investigated by activated carbon impregnated with TiO2. Emphasis was given on the effect of different parameters, such as composite type, initial Ibuprofen concentration (5-25 mg/L), temperature (22-28 °C) and pH (acidic and alkaline solution). The experiment was carried out in a self-made tubular flow reactor, with one 15 W monochromatic UV lamp (254 nm). The composite AC90T10 gives the highest removal degree of 92% of Ibuprofen solution under UV light within 4 h, due to synergy of adsorption and photodegradation. It was found that weight ratio of composite/Ibuprofen has limited effect on the removal degree within the concentration range (5-25 mg/L), but reaction time under UV light (4 h) and pH (acidic solution) are very important. The kinetic experimental data obtained at pH 4.3 at 25 °C on different composites were fitted to pseudo-first, pseudo-second and Elovich models, obtaining a high accuracy based on R2 values. From the results, composites of granular activated carbon and TiO2 can enhance removal of Ibuprofen effectively, making recycle process much easier and less costly, which can be a promising method in future water treatment.

Surface-modified three-dimensional graphene nanosheets as a stationary phase for chromatographic separation of chiral drugs.

Carbon-based stationary phases for chromatographic separation have been commercially available since the 1980s. Porous graphitic carbon liquid chromatography columns are known to be highly resistant to aggressive mobile phases and extreme pH values of solvents and eluents, an important advantage compared to conventional silica-based alternatives. In our work, we demonstrate a new variant of carbon-based stationary phases for liquid chromatography, specifically developed for chiral separation. Mesoporous three-dimensional graphene nanosheets (3D GNS), functionalized with tetracyanoethylene oxide (TCNEO) and (S)-(+)-2-pyrrolidinemethanol, demonstrate pharmaceutical-grade chiral separation of model ibuprofen and thalidomide racemic mixtures when used as Chiral Stationary Phases (CSPs), with performance parameters comparable to currently commercially available CSPs. Simple covalent attachment of functionalization groups to the surface of mesoporous three-dimensional graphene nanosheets makes these carbon-based CSPs chemically stable and up to an order of magnitude less expensive than standard silica-based analogues.

Solid-phase extraction of drugs with cuttlefish bone powder as a sorbent.

We investigated cuttlefish bone powder for the solid-phase extraction of naproxen, ibuprofen, and carbamazepine. The basic principles controlling the extraction are presented to aid in the choice of the nature and quantity of the extracting phase according to the sample matrix and the solute properties, based on the mechanisms of phase retention. Their retention mechanism is based on hydrogen bonding and electrostatic interactions. The results show a significant recovery rate for the three drugs, selectivity, and low cost. The method has successfully reduced the amount of tested pharmaceuticals with recoveries >87% at pH 4.

Use of Polymer Inclusion Membranes (PIMs) as support for electromembrane extraction of non-steroidal anti-inflammatory drugs and highly polar acidic drugs.

The use of polymer inclusion membranes (PIMs) as support of 1-octanol liquid membrane in electromembrane extraction (EME) procedure is proposed. Synthesis of PIMs were optimized to a composition of 29% (w/w) of cellulose triacetate as base polymer and 71% (w/w) of Aliquat®336 as cationic carrier. Flat PIMs of 25µm thickness and 6mm diameter were used. EME protocol was implemented for the simultaneous extraction of four non-steroidal anti-inflammatory drugs (NSAIDs) (salicylic acid, ketoprofen, naproxen and ibuprofen) and four highly polar acidic drugs (anthranilic acid, nicotinic acid, amoxicillin and hippuric acid). Posterior HPLC separation of the extracted analytes was developed with diode array detection. Recoveries in the 81-34% range were obtained. EME procedure was applied to human urine samples.

Nitrate removal from pharmaceutical wastewater using microbial electrochemical system supplied through low frequency-low voltage alternating electric current.

In this study, a microbial electrochemical system (MES) was designed to evaluate the effects of a low frequency-low voltage alternating electrical current on denitrification efficacy in the presence of ibuprofen as a low biodegradable organic carbon source. Cylindrical carbon cloth and stainless steel mesh electrodes containing a consortium of heterotrophic and autotrophic bacteria were mounted in the wall of the designed laboratory-scale bioreactor. The effects of inlet nitrate concentration (50-800mgL-1), retention time (2.5-24h), waveform magnitude (0.1-9.6Vp-p), adjustable direct current voltage added to offset voltage (0.1-4.9V), alternating current frequency (10-60Hz), and waveforms (sinusoidal, square, and ramp) were studied in this work. The results showed that the proposed system removes 800mgL-1 nitrate up to 95% during 6.5h. Optimum conditions were obtained in the 8Vp-p using a frequency of 10Hz of a sinusoidal waveform. The morphology studies confirmed bacterial morphology change when applying the alternating current. Dehydrogenase activity of biofilms formed on surface of stainless steel electrodes increased to 15.24µgTFmgbiomasscm-2d. The maximum bacterial activity was obtained at a voltage of 8Vp-p. The experimental results revealed that the MES using a low frequency-low voltage alternating electrical current is a promising technique for nitrate removal from pharmaceutical wastewaters in the presence of low biodegradability of carbon sources such as ibuprofen.