Occurrence, toxicity, impact and removal of selected non-steroidal anti-inflammatory drugs (NSAIDs): A review.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used pharmaceuticals for human therapy, pet therapeutics, and veterinary feeds, enabling them to enter into water sources such as wastewater, soil and sediment, and seawater. The control of NSAIDs has led to the advent of the novel materials for treatment techniques. Herein, we review the occurrence, impact and toxicity of NSAIDs against aquatic microorganisms, plants and humans. Typical NSAIDs, e.g., ibuprofen, ketoprofen, diclofenac, naproxen and aspirin were detected at high concentrations in wastewater up to 2,747,000 ng L-1. NSAIDs in water could cause genotoxicity, endocrine disruption, locomotive disorders, body deformations, organs damage, and photosynthetic corruption. Considering treatment methods, among adsorbents for removal of NSAIDs from water, metal-organic frameworks (10.7-638 mg g-1) and advanced porous carbons (7.4-400 mg g-1) were the most robust. Therefore, these carbon-based adsorbents showed promise in efficiency for the treatment of NSAIDs.

Effect of biosolids amendment on the fate and mobility of non-steroidal anti-inflammatory drugs (NSAIDs) in a field-based lysimeter cell study.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used globally to treat and prevent illness. Biosolids change physico-chemical characteristics of soil and can affect the mobility of NSAIDs. A field-based lysimeter study evaluated the effect of three rates (0, 7, and 28 Mg ha-1) of alkaline treated biosolids (ATB) on the leaching potential of naproxen (NPX), ibuprofen (IBF), and ketoprofen (KTF) over 34 days in a sandy loam textured soil. Although all three NSAIDs in the lysimeter cells vertically migrated to deeper soil depths after spiking, the sum of all NPX, IBF, and KTF detected in the leachate samples from all treatments were only 0.03%, 0.02%, and 0.04% of the initial spiking mass to the surface soil, respectively. A mass balance analysis indicated a low accumulation of these compounds in the soil at the end of the study (Day 34) from all treatments with only 4.8%, 0.5%, and 0.7% of initial spiked NPX, IBF, and KTF, respectively. Application of ATB significantly increased soil pH and organic matter (OM) content of the soils but did not impact retention of the compounds in the soil profile. Overall, all three NSAIDs in the present study presented low mobility in the loamy sand textured agricultural soil.

Literature Review: Evaluation of Drug Removal Techniques in Municipal and Hospital Wastewater.

There are several techniques for the removal of pharmaceuticals (drugs) from wastewater; however, strengths and weaknesses have been observed in their elimination processes that limit their applicability. Therefore, we aimed to evaluate the best techniques for the removal of pharmaceuticals from municipal and hospital wastewater. For this, a non-experimental, descriptive, qualitative-quantitative design was used, corresponding to a systematic review without meta-analysis. Based on established inclusion and exclusion criteria, 31 open-access articles were selected from the Scopus, ProQuest, EBSCOhost, and ScienceDirect databases. The results showed that high concentrations of analgesics such as naproxen (1.37 mg/L) and antibiotics such as norfloxacin (0.561 mg/L) are frequently found in wastewater and that techniques such as reverse osmosis, ozonation, and activated sludge have the best removal efficiency, achieving values of 99%. It was concluded that reverse osmosis is one of the most efficient techniques for eliminating ofloxacin, sulfamethoxazole, carbamazepine, and diclofenac from municipal wastewater, with removal rates ranging from 96 to 99.9%, while for hospital wastewater the activated sludge technique proved to be efficient, eliminating analgesics and antibiotics in the range of 41-99%.

Effective adsorption of diclofenac and naproxen from water using fixed-bed column loaded with composite of heavy sugarcane ash and polyethylene terephthalate.

The contamination of water by pharmaceutical pollutants is a major issue these days due to excessive use of these ingredients in modern life. This study evaluated the adsorption and effectiveness of a low-cost composite prepared from heavy sugarcane ash (HSA) fused with polyethylene terephthalate (PET) and functionalized with iron (Fe3+) in a dynamic system through a fixed-bed column. The solution of synthetic drugs was prepared and placed in a reservoir, using a peristaltic pump the solution is run onto the fixed bed column at a flow rate of 2 mL min-1. Saturation time and adsorption capacity were evaluated by centrifugation and extraction after a regular interval of 2 h from the adsorption column. The samples were analyzed using high-performance liquid chromatography (HPLC) and the data was modeled for quantification. For DIC removal, an adsorption capacity of 324.34 µg. g-1 and a saturation time of 22 h were observed, while the adsorption capacity of NAP was 956.49 µg. g-1, with a saturation time of 8 h. Thus, the PETSCA/Fe3+ adsorbent proved to be quite efficient for removing the pharmaceutical pollutants, with a longer period of operation for DIC removal. These findings suggested that a highly efficient bed column made from a less expensive waste material and could be used to remove hazardous pharmaceutical contaminants.

Design and application of molecularly imprinted polymers for adsorption and environmental assessment of anti-inflammatory drugs in wastewater samples.

In this study, a series of molecularly imprinted polymers (MIPs) have been synthesized using separately diclofenac, naproxen, and ibuprofen as templates with three different polymerization approaches. Two functional monomers, methacrylic acid (MAA) and 2-vinylpyridine (2-VP), were tested and ethylene glycol dimethacrylate (EGDMA) was used as crosslinker; also, template-free polymers (NIPs) were synthesized. It was found that the MIP with the highest retention percentage for diclofenac was the one prepared by the emulsion approach and with MAA (98.3%); for naproxen, the one prepared by the bulk polymerization with MAA (99%); and for ibuprofen, the one synthesized by bulk with 2-VP (97.7%). These three MIPs were characterized by scanning electron microscopy, thermogravimetric test, Fourier transform infrared, specific area measurements, and surface charge. It was found that the emulsion method allowed particle size control, while the bulk method gave heterogeneous particles. The three evaluated MIPs exhibited thermal stability up to 300 °C, and it was observed that 2-VP confers greater stability to the material. From the BET analysis, it was demonstrated that the MIPs and NIPs evaluated are mesoporous materials with a pore size between 10 and 20 nm. In addition, the monomer influenced the surface charge of the material, since the MAA conferred an acidic point of zero charge (PZC), while the 2-VP conferred a PZC of basic character. Through adsorption isotherms, it was determined  that there is a higher adsorption capacity of the MIPs at acidic pH following a pseudo-second-order kinetic model. Finally, the MIPs were used to determine the non-steroidal anti-inflammatory drugs (NSAIDs) understudy in San Luis Potosí, México, wastewater, finding concentrations of 0.642, 0.985, and 0.403 mg L-1 for DCF, NPX, and IBP, respectively.

From the pills to environment - Prediction and tracking of non-steroidal anti-inflammatory drug concentrations in wastewater.

The extend of environment pollution by pharmaceuticals is in a stage that required more automatic and integrated solutions. The non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most popular pharmaceutical in the world and emerging pollutants of natural waters. The aim of the paper was to check the correlation of the sales data of selected NSAIDs (ibuprofen, naproxen, diclofenac) and their concentration in the WWTP in order to enable predicting their loads, having only the sales data. For calculations, we apply three discharge scenarios (the fates between purchased to the presence in influents), having in mind that some part of sold mass can be improperly dispose to sewage system. To support predictions, chemical analysis was conducted in two conventional wastewater treatment plants (WWTPs) located in Poland during 2018 and 2020, thereby before and during pandemic situation. The NSAIDs concentration in the influent was higher than that which would be obtained if all of the administrated mass of the pharmaceutical went through the metabolic pathway of transformation. This means that substantial mass of sold NSAIDs in improperly dispose to sewage system, and this factor need to be taken into account in future predictions. Furthermore, results indicate that the variance of naproxen and diclofenac concentrations in the influent has no correlation with relatively stable sales throughout whole year. The pandemic situation had yet no direct effect to diclofenac concentrations in influents, despite observed increasing of sales. It was calculated that more than 60 kg of diclofenac was discharged into the Baltic Sea in 2018, and 20 kg in the first half of 2021 from two tested WWTPs. The presence of 4OH-diclofenac in effluents often in higher concentration compared to diclofenac mean that this still biologically active compound need to be taken into account in future risk assessment.

Pharmaceuticals as emerging pollutants: Case naproxen an overview.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including naproxen (NP), diclofenac, ibuprofen, etc., are widely used for fever and pain relief. NP is one of the most widely consumed drugs in the world, because it is available over the counter in many countries. Many studies have proven that NP is not eliminated in conventional water treatment processes and its biodegradation in the environment is also difficult compared to other drugs. Along these lines, we are aware that both the original compound and its metabolites can be found in different destinations in the environment. To assess the environmental exposure and the risks associated with NP, it is important to understand better the environment where they finally reach, the behavior of its original compounds, its metabolites, and its transformation products. In this sense, the purpose of this review is to summarize the current state of knowledge about the introduction and behavior of NP in the environments they reach and highlight research needs and gaps. Likewise, we present the sources, environmental destinations, toxicology, environmental effects, and quantification methodologies.

A review on environmental occurrence, toxicity and microbial degradation of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs).

In recent years, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have surfaced as a novel class of pollutants due to their incomplete degradation in wastewater treatment plants and their inherent ability to promote physiological predicaments in humans even at low doses. The occurrence of the most common NSAIDs (diclofenac, ibuprofen, naproxen, and ketoprofen) in river water, groundwater, finished water samples, WWTPs, and hospital wastewater effluents along with their toxicity effects were reviewed. The typical concentrations of NSAIDs in natural waters were mostly below 1 µg/L, the rivers receiving untreated wastewater discharge have often showed higher concentrations, highlighting the importance of effective wastewater treatment. The critical analysis of potential, pathways and mechanisms of microbial degradation of NSAIDs were also done. Although studies on algal and fungal strains were limited, several bacterial strains were known to degrade NSAIDs. This microbial ability is attributed to hydroxylation by cytochrome P450 because of the decrease in drug concentrations in fungal cultures of Phanerochaete sordida YK-624 on incubation with 1-aminobenzotriazole. Moreover, processes like decarboxylation, dehydrogenation, dechlorination, subsequent oxidation, demethylation, etc. also constitute the degradation pathways. A wide array of enzymes like dehydrogenase, oxidoreductase, dioxygenase, monooxygenase, decarboxylase, and many more are upregulated during the degradation process, which indicates the possibility of their involvement in microbial degradation. Specific hindrances in upscaling the process along with analytical research needs were also identified, and novel investigative approaches for future monitoring studies are proposed.

Occurrence and ecotoxicological risk assessment of non-steroidal anti-inflammatory drugs in South African aquatic environment: What is known and the missing information?

Non-steroidal anti-inflammatory drugs (NSAIDs) are medications used individually or as mixtures with other pharmaceuticals for the treatment of various illnesses. Their easy accessibility and high human consumption have resulted to their detection at high concentrations in South African water resources. In the present work, an extensive review of the occurrence and ecotoxicological risk assessment of NSAIDs in South African aquatic environment is provided. Reviewed literature suggested ibuprofen, naproxen, diclofenac, ketoprofen and fenoprofen as the most prominent NSAIDs in the South African aquatic environment. Among these NSAIDs, higher concentrations of ibuprofen are common in South African waters. As a result, this drug was found to pose high ecotoxicological risks towards the aquatic organisms with the highest risk quotients of 14.9 and 11.9 found for algae in surface water and wastewater, respectively. Like in other parts of the world, NSAIDs are not completely removed in wastewater treatment plants. Removal efficiencies below 0% due to higher concentrations of NSAIDs in wastewater effluents rather than influents were observed in certain instances. The detection of NSAIDs in sediments and aquatic plants could serve as the important starting step to investigate other means of NSAIDs removal from water. In conclusion, recommendations regarding future studies that could paint a clearer picture regarding the occurrence and ecotoxicological risks posed by NSAIDs in South African aquatic environment are provided.

Core-shell MOF@COFs used as an adsorbent and matrix for the detection of nonsteroidal anti-inflammatory drugs by MALDI-TOF MS.

A core-shell material (UiO@TapbTp) has been developed as an adsorbent and matrix to detect nonsteroidal anti-inflammatory drugs (NSAIDS) by matrix laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in complex samples. The hybrid material is prepared by growing covalent organic framework (COF, TapbTp) layers in situ on an amino-modified metal-organic framework (MOF, UiO-66-NH2). The combination of the MOF and COF overcomes their individual shortcomings and integrates both of their advantages. Compared with the bare COF and MOF, the core-shell composite exhibits improved enrichment ability and matrix performance. With the help of pre-enrichment under optimized conditions, the limits of detection (LODs) for ketoprofen, naproxen, and aspirin are reduced by nearly 1000 times, with values of 0.001 mg L-1, 0.010 mg L-1, and 0.001 mg L-1, respectively, and the relative standard deviations (RSDs) are all below 12.35%. The good recoveries (84.8-118%) in (spiked) saliva and environmental water sample further verify the applicability of the method in complex samples.

Solidified floating organic drop microextraction (SFODME) for the simultaneous analysis of three non-steroidal anti-inflammatory drugs in aqueous samples by HPLC.

In this work, a liquid-liquid microextraction methodology using solidified floating organic drop (SFODME) was combined with liquid chromatography and UV/Vis detection to determine non-steroidal anti-inflammatory drugs (NSAIDs) naproxen (NPX), diclofenac (DCF), and mefenamic acid (MFN) in tap water, surface water, and seawater samples. Parameters that can influence the efficiency of the process were evaluated, such as the type and volume of the extractor and dispersive solvents, effect of pH, agitation type, and ionic strength. The optimized method showed low detection limits (0.09 to 0.25 µg L-1), satisfactory recovery rates (90 to 116%), and enrichment factors in the range between 149 and 199. SFODME showed simplicity, low cost, speed, and high concentration capacity of the analytes under study. Its use in real samples did not demonstrate a matrix effect that would compromise the effectiveness of the method, being possible to apply it successfully in water samples with different characteristics.

UV-visible photodegradation of naproxen in water - Structural elucidation of photoproducts and potential toxicity.

The UV-visible photodegradation of Naproxen (6-methoxy-α-methyl-2-naphthaleneacetic acid, CAS: 22204-53-1), one of the most used and detected non-steroidal anti-inflammatory drugs (NSAIDs) in the world, and its ecotoxicological consequences were investigated in an aqueous medium. The photo-transformation products were analyzed and the structures of photoproducts were elucidated using gas chromatography coupled with tandem mass spectrometry (GC-MS/MS) and high-performance liquid chromatography coupled with ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (LC-FTICR-MS). Seven photoproducts were detected and characterized, photo-transformation mechanisms have been postulated to rationalize their formation under irradiation. In silico Q.S.A.R. (Quantitative Structure-Activity Relationship) toxicity predictions were performed with the Toxicity Estimation Software Tool (T.E.S.T.) and in vitro assays were carried out on Vibrio fischeri bacteria. Some of the obtained photoproducts exhibit higher potential toxicity than Naproxen itself but the whole toxicity of the irradiated solution is not of major concern.

Optimization and application of hollow fiber liquid-phase microextraction and microwave-assisted extraction for the analysis of non-steroidal anti-inflammatory drugs in aqueous and plant samples.

Human consumption of non-steroidal anti-inflammatory drugs (NSAIDs) is increasing, which poses a great risk of pollution by these pharmaceuticals on the aquatic environment. Therefore, this study reports the optimization of microwave-assisted extraction using water as a green solvent and hollow fiber liquid-phase microextraction (HF-LPME) methods followed by high-performance liquid chromatography-high resolution mass spectrometry analysis of NSAIDs in wastewater and aquatic plant, Eichhornia crassipes. The optimized MAE resulted in efficient transfer of selected NSAIDs from plant samples into the aqueous phase yielding the recoveries ranging from 91 to115%. A multivariate approach based on half fractional factorial and central composite design was used during the optimization of HF-LPME. Under the optimized conditions, the maximum enrichment factors for naproxen, fenoprofen, diclofenac, and ibuprofen were 49, 126, 93 and 156, respectively. The overall analytical method recoveries ranged from 86 to 116% while the limits of quantitation for wastewater and plant samples ranged from 0.09 to 0.59 µg L-1 and from 0.11 to 0.59 µg kg-1, respectively. The precision of the proposed analytical method which was measured in terms of RSD values did not exceed 5%. Naproxen was the most abundant compound in both wastewater and the Eichhornia crassipes plant samples with concentrations of up to 3.30 µg L-1 and 10.97 µg kg-1, respectively. The detection of NSAIDs in Eichhornia crassipes means this plant has the ability to bioaccumulate pharmaceutical load in surface water.

Effects of chronic exposure to a pharmaceutical mixture on the three-spined stickleback (gasterosteus aculeatus) population dynamics in lotic mesocosms.

Pharmaceutical substances are ubiquitous in the aquatic environment and their concentration levels typically range from ng/L up to several µg/L. Furthermore, as those compounds are designed to be highly biologically active, assessing their impacts on non-target organisms is important. Here, we conducted a mesocosm experiment testing a mixture of five pharmaceuticals (diclofenac, carbamazepine, irbesartan, acetaminophen and naproxen) on fish, three-spined stickleback (Gasterosteus aculeatus). The mixture concentration levels were chosen on the basis of the contamination of the Meuse river in Belgium which had been measured previously during a monitoring campaign undertaken in 2015 and 2016. Three nominal mixture concentration levels were tested: the lowest concentration level mixture was composed by environmentally-relevant concentrations that approximate average realistic values for each pharmaceuticals (Mx1); the two other levels were 10 and 100 times these concentrations. Although no impact on stickleback prey was observed, the mixture significantly impaired the survival of female fish introduced in the mesocosms at the highest treatment level without causing other major differences on fish population structure. Impacts on condition factors of adults and juveniles were also observed at both individual and population levels. Using a modelling approach with an individual-based model coupled to a bioenergetic model (DEB-IBM), we concluded that chronic exposure to environmentally-relevant concentrations of five pharmaceuticals often detected in the rivers did not appear to strongly affect the three-spined stickleback populations. Mechanisms of population regulation may have counteracted the mixture impacts in the mesocosms.

Electrochemical analysis of naproxen in water using poly(l-serine)-modified glassy carbon electrode.

A poly(l-serine)-modified glassy carbon electrode (PLS/GCE) was fabricated by electropolymerization and used to study the detection of naproxen (NPX), a representative non-steroidal anti-inflammatory drug, in phosphate buffer supporting electrolyte at pH 5.0. Results indicated that the PLS/GCE was capable of determination of NPX at a working potential of 0.92 (vs. Ag/AgCl) in voltammetry mode. Experimental factors such as scan rate, accumulation time, solution pH, initial NPX concentration, and interferences were optimized for NPX determination efficiency. The morphology and elemental distribution of the electrode surface were characterized by ESEM, TEM, PSD, XRD, FTIR, TGA, XPS, and zeta potential. NPX oxidation current increased with increasing analyte concentration and scan rate but decreased with increasing pH. Linear sweep voltammetry calibration curve was established in the NPX concentration range of 4.3-65 µM, with detection limit and average recovery of 0.69 µM (n = 3) and 104 ± 2.5%, respectively. PLS/GCE is simple, accurate, reproducible, and easy for operation, therefore would be cost-effective for the determination of NPX.

Chiral molecularly imprinted polymeric stir bar sorptive extraction for naproxen enantiomer detection in PPCPs.

Chiral micropollutant analysis in pharmaceuticals and personal care products (PPCPs) is interesting but challenging. We firstly developed a series of chiral molecularly imprinted polymeric (CMIP) stir bar sorptive extraction coatings by combining a chiral template with chiral functional monomers via a click reaction for naproxen enantiomer analysis in PPCPs. Heterochiral selectivity was observed in the molecule recognition of the CMIP coatings, which demonstrated good adsorption capability for the chiral template and its structurally similar chiral compounds. The coatings also exhibited excellent enrichment capability for chiral analytes in an aqueous matrix. The surface morphology and pore structure of the CMIP coatings were characterized. The molecular interactions between the chiral template and chiral functional monomer were investigated through UV-vis spectroscopy and theoretical calculations to prove the effective interactions existing in the heterochiral MIPs. The CMIP coatings were used to enrich naproxen enantiomers in chiral drug and environmental water samples, and satisfactory recoveries (83.98 %-118.88 %) with a relative standard deviation of 3.49 %-13.08 % were achieved. The heterochiral imprinted coating-based method provided a sensitive, selective, and effective enrichment strategy for chiral micropollutant analysis in PPCPs. This technique is critical for chiral molecule recognition and enantiomer analysis in complex samples.

Graphene-Oxide-Based Electrochemical Sensors for the Sensitive Detection of Pharmaceutical Drug Naproxen.

Here we report on a selective and sensitive graphene-oxide-based electrochemical sensor for the detection of naproxen. The effects of doping and oxygen content of various graphene oxide (GO)-based nanomaterials on their respective electrochemical behaviors were investigated and rationalized. The synthesized GO and GO-based nanomaterials were characterized using a field-emission scanning electron microscope, while the associated amounts of the dopant heteroatoms and oxygen were quantified using x-ray photoelectron spectroscopy. The electrochemical behaviors of the GO, fluorine-doped graphene oxide (F-GO), boron-doped partially reduced graphene oxide (B-rGO), nitrogen-doped partially reduced graphene oxide (N-rGO), and thermally reduced graphene oxide (TrGO) were studied and compared via cyclic voltammetry (CV) and differential pulse voltammetry (DPV). It was found that GO exhibited the highest signal for the electrochemical detection of naproxen when compared with the other GO-based nanomaterials explored in the present study. This was primarily due to the presence of the additional oxygen content in the GO, which facilitated the catalytic oxidation of naproxen. The GO-based electrochemical sensor exhibited a wide linear range (10 mM-1 mM), a high sensitivity (0.60 µAµM-1cm-2), high selectivity and a strong anti-interference capacity over potential interfering species that may exist in a biological system for the detection of naproxen. In addition, the proposed GO-based electrochemical sensor was tested using actual pharmaceutical naproxen tablets without pretreatments, further demonstrating excellent sensitivity and selectivity. Moreover, this study provided insights into the participatory catalytic roles of the oxygen functional groups of the GO-based nanomaterials toward the electrochemical oxidation and sensing of naproxen.

Naproxen in the environment: its occurrence, toxicity to nontarget organisms and biodegradation.

This article summarizes the current knowledge about the presence of naproxen in the environment, its toxicity to nontarget organisms and the microbial degradation of this drug. Currently, naproxen has been detected in all types of water, including drinking water and groundwater. The concentrations that have been observed ranged from ng/L to µg/L. These concentrations, although low, may have a negative effect of long-term exposure on nontarget organisms, especially when naproxen is mixed with other drugs. The biological decomposition of naproxen is performed by fungi, algae and bacteria, but the only well-described pathway for its complete degradation is the degradation of naproxen by Bacillus thuringiensis B1(2015b). The key intermediates that appear during the degradation of naproxen by this strain are O-desmethylnaproxen and salicylate. This latter is then cleaved by 1,2-salicylate dioxygenase or is hydroxylated to gentisate or catechol. These intermediates can be cleaved by the appropriate dioxygenases, and the resulting products are incorporated into the central metabolism. KEY POINTS: •High consumption of naproxen is reflected in its presence in the environment. •Prolonged exposure of nontargeted organisms to naproxen can cause adverse effects. •Naproxen biodegradation occurs mainly through desmethylnaproxen as a key intermediate.

Biological removal of pharmaceuticals by Navicula sp. and biotransformation of bezafibrate.

Pharmaceutically active compounds are of great concern due to their detection frequency in the environment and the unexpected risks. In this study, the simultaneous removal of mixed pharmaceuticals by microalgae was explored using a typical freshwater diatom Navicula sp. Results showed that Navicula sp. could efficiently remove atenolol, carbamazepine, ibuprofen and naproxen with the efficiencies of >90% after 21 d of exposure. As compared to the removal efficiencies of each pharmaceutical in the individual pharmaceutical treatments, the degradation of sulfamethoxazole, bezafibrate, and naproxen was improved in the mixed treatment, whereas the removal efficiencies of carbamazepine and atenolol decreased. Additionally, the presence of hydrophobic pharmaceuticals (i.e., ibuprofen and naproxen) accelerated the degradation of carbamazepine and sulfamethoxazole and inhibited the removal of atenolol in the mixture with the combination of six pharmaceuticals, while the addition of other pharmaceuticals show no significant effect on the removal of ibuprofen and naproxen. The bioaccumulation of pharmaceuticals in Navicula sp. increased as their log KOW values decreased. Four bezafibrate metabolites were identified and the degradation pathways of bezafibrate in diatom were proposed. It is the first report on the metabolism of BEZ in diatom, and further studies on the environmental risk of the metabolites should be investigated.