ReviewNon-steroidal anti-inflammatory drugs in the environment: Where were we and how far we have come?☆
Graphical abstract
Introduction
In the recent decade, there has been an increasing interest in emerging contaminants (ECs) including, pharmaceutically active compounds, endocrine-disrupting chemicals and personal care products (PCPs) (Boix et al., 2016; Tran et al., 2018) (Petrie et al., 2015). The main threat of mentioned classes of ECs is due to missing information, regarding their environmental and human toxicological effects, as well as an understudied area of detection, analysis and removal methods (Yu et al., 2011). The initial classification of pharmaceuticals and PCPs as major and concerning pollutants was proposed by Daughton and Ternes (1999) (Daughton and Ternes, 1999), which was followed by advancements in analytical procedures and the growing development of environmental matrices. An increased concern in recent years is directed towards active pharmaceutical ingredients (APIs), that are identified at trace level in surface waters, sewage and wastewater treatment plants (WWTPs) effluents which eventually returns to human bodies (Daughton and Ternes, 1999), due to their high stability in chemical structure as well as highly active functional molecule groups (Tyumina et al., 2020). Due to the lack of knowledge on the analytical techniques in detection, these groups of emerging contaminants, enter the environment without any control or regulation (Barroso et al., 2019). The non-steroidal anti-inflammatory pharmaceuticals (NSAIDs) are one of the most frequently used pharmaceuticals internationally, and listed among the top 10 persistent pollutants (Green, 2001). Among the NSAIDs, the most recurrently detected in the environment includes diclofenac (DCF), ibuprofen (IBP) and naproxen (NPX) recognized as potential ECs with high-octanol partition coefficient and low pKa values (Table 1). These specific drugs reduce inflammation and pain by blocking COX enzymes and prostaglandin production. Standard biological actions and body maintenance roles are directly related to cyclooxygenase (COX) activity and prostaglandins, wherein analgesia and anti-inflammation are achieved through induction. Prostaglandins (lipid autacoids resulting from arachidonic acids) are strong intermediaries of inflammation that cause edema, pain, and vasodilation. The mechanism of action of these drugs is indicated in supplementary data (Figure S1). Consequently, a great capacity to passively diffuse through biological membranes, with an elevated persistence in aquatic environments, is observed in these pharmaceuticals (Almeida et al., 2017; Green, 2001; Jiang et al., 2017).
This review aims to drive the focus on adopting a novel challenge-driven approach towards determination, monitoring and removal of NSAIDs. Previous studies investigated the occurrence, fate and removal of EC’s and pharmaceuticals in general, however, the elimination of NSAIDs residuals in the environment demands exclusive research (Feng et al., 2013) (Tanwar et al., 2015) (Tijani et al., 2013). This paper summarizes current knowledge on determination, detection, fate and occurrence along with the removal of NSAIDs in the environment particularly in WWTPs, with a great emphasis on innovative and advanced tools and technologies. Additionally, previous reviews, lack a focus on current policies and regulations on the usage and release of NSAIDs in the environment. This review paper investigates the available data and policies to formulate guidance for further regulation of NSAIDs in the environment. The final objective was to recognize knowledge scarcities and put forward research guidelines for upcoming investigations.
Section snippets
Wastewater (WW), surface water, groundwater and drinking water
NSAIDs are commonly used across the world and have been released in a range of millions of tons back into the environment with high concentrations of these pollutants accumulated in treatment systems (Fent et al., 2006) (Żur et al., 2018) (Li, 2014). The concentration levels vary from one country to another based on the drug consumption and usage pattern, population and efficiency of treatment plants (Tijani et al., 2013). Moreover, there is comparable difference between number of studies on
Biological samples
In general, drug analysis follows a three-step procedure: extraction-separation-detection. Several studies mark the extraction/sample pretreatment phase of NSAIDs analysis as complicated, especially in the case of biological fluids, due to the complex nature of samples and the relatively low concentration of target analytes (Farajzadeh et al., 2015), (Martinez-Sena et al., 2016), (Sarafraz-Yazdi et al., 2012). Furthermore, multi-residue analysis of drugs is likewise challenging because of the
Policy on EC management and related constraining circumstances
The postponement of regulations and laws concerning the assessment of adverse environmental and health effects of pharmaceutical as emerging pollutants have drawn attention by concerned parties, although regulations have never kept the pace of industrial and technological developments specifically in the case of groundwater (Naidu et al., 2016).
Several matters are holding down the policymaking process such as lack of knowledge and regulations as well as increasing the expansion of new
Discussion and future work
NSAIDs presence in any aquatic or soil environment has the potential to alter the diversity, biomass composition, biochemical reactions, metabolic and enzymatic activity of the microbiological community (Cycon et al., 2016), which inhibits the presence of indigenous species and alters key ecological processes. This review shows the limited data and studies available on NSAIDs as emerging contaminants and the other hand, the crucial need to develop the dataset for human health risk assessment
Conclusion
NSAIDs have been used as anti-inflammatory drugs and have been present in the aquatic and solid environmental matrices for decades and life has been exposing to it. Recently, the detection, quantification and removal of these compounds have grown by excessive research efforts, devoted to study the occurrence of ECs and the effective removal methods. However, for the prediction of these micropollutant impacts on the environment, comprehensive modeling of NSAID fate is required. Overall,
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
The authors appreciate recognizing the Ontario Graduate Scholarship (OGS), James and Joanne Love Chair in Environmental Engineering and Seed Fund, York University, Toronto, ON, Canada for their endless support and interest at each point of this research.
References (172)
- et al.
Chemosphere Biodegradation of persistent organics can overcome adsorption e desorption hysteresis in biological activated carbon systems
Chemosphere
(2016) - et al.
Progress in the biological and chemical treatment technologies for emerging contaminant removal from wastewater: a critical review
J. Hazard Mater.
(2017) - et al.
Occurrence of pharmaceutically active and non-steroidal estrogenic compounds in three different wastewater recycling schemes in Australia
Chemosphere
(2007) - et al.
Magnetic nanoparticles based dispersive micro-solid-phase extraction as a novel technique for coextraction of acidic and basic drugs from biological fluids and waste water
J. Chromatogr. A
(2014) - et al.
Development of electrochemically controlled packed-in-tube solid phase microextraction method for sensitive analysis of acidic drugs in biological samples
Talanta
(2018) - et al.
Development and validation of a liquid chromatography-electrospray ionization-tandem mass spectrometry method for the determination of urolithin C in rat plasma and its application to a pharmacokinetic study
J. Pharmaceut. Biomed. Anal.
(2016) - et al.
Occurrence and removal of antibiotics, hormones and several other pharmaceuticals in wastewater treatment plants of the largest industrial city of Korea
Sci. Total Environ.
(2011) - et al.
Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans
Gastroenterology
(1993) - et al.
Behaviour of emerging contaminants in sewage sludge after anaerobic digestion
Chemosphere
(2016) - et al.
Capillary electrophoresis assay of netilmicin sulphate
J. Pharmaceut. Biomed. Anal.
(2005)
Factory-discharged pharmaceuticals could be a relevant source of aquatic environment contamination: review of evidence and need for knowledge
Chemosphere
A new molecularly imprinted polymer for the selective extraction of naproxen from urine samples by solid-phase extraction
J. Chromatogr. B Anal. Technol. Biomed. Life Sci.
Degradation of 32 emergent contaminants by UV and neutral photo-fenton in domestic wastewater effluent previously treated by activated sludge
Water Res.
Solid-phase microextraction and chiral HPLC analysis of ibuprofen in urine
J. Chromatogr. B Anal. Technol. Biomed. Life Sci.
A validated GC-MS method for the determination and quantification of residual solvents in counterfeit tablets and capsules
J. Pharmaceut. Biomed. Anal.
Prognostic impact of cyclooxygenase-2 in breast cancer
Clin. Breast Canc.
Development and validation of a confirmatory method for the determination of 12 non steroidal anti-inflammatory drugs in milk using liquid chromatography-tandem mass spectrometry
J. Chromatogr. A
An LC-MS/MS procedure for the quantification of naproxen in human plasma: development, validation, comparison with other methods, and application to a pharmacokinetic study
J. Chromatogr. B Anal. Technol. Biomed. Life Sci.
First interlaboratory exercise on non-steroidal anti-inflammatory drugs analysis in environmental samples
Talanta
Removal of residual anti-inflammatory and analgesic pharmaceuticals from aqueous systems by electrochemical advanced oxidation processes
A review. Chem. Eng. J.
Ecotoxicology of human pharmaceuticals
Aquat. Toxicol.
Ecotoxicological impact of pharmaceuticals found in treated wastewaters: study of carbamazepine, clofibric acid, and diclofenac
Ecotoxicol. Environ. Saf.
Occurrence and concentrations of pharmaceutical compounds in groundwater used for public drinking-water supply in California
Sci. Total Environ.
Occurrence and fate of emerging contaminants in water environment: a review
Groundw. Sustain. Dev.
Presence and biological effects of emerging contaminants in Llobregat River basin: a review
Environ. Pollut.
Occurrence and removal of pharmaceuticals in wastewater treatment plants at the Spanish Mediterranean area of Valencia
Chemosphere
Understanding NSAIDs: from aspirin to COX-2
Clin. Cornerstone
Organic chemicals in sewage sludges
Sci. Total Environ.
Environmental risk assessment of pharmaceutical residues in wastewater effluents, surface waters and sediments
Talanta
Fast ibuprofen, ketoprofen and naproxen simultaneous determination in human serum for clinical toxicology by GC-FID
Clin. Biochem.
Determination of non-steroidal anti-inflammatory drugs residues in animal muscles by liquid chromatography-tandem mass spectrometry
Anal. Chim. Acta
The removal of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs during wastewater treatment and its impact on the quality of receiving waters
Water Res.
Removal of non-steroidal anti-inflammatory drugs (NSAIDs) and carbamazepine from wastewater using water-soluble protein extracted from Moringa stenopetala seeds
J. Environ. Chem. Eng.
Pharmaceuticals, hormones and bisphenol A in untreated source and finished drinking water in Ontario, Canada - occurrence and treatment efficiency
Sci. Total Environ.
Determination of non-steroidal anti-inflammatory drug (NSAIDs) residues in water samples
Environ. Int.
Fate of pharmaceuticals and personal care products in a wastewater treatment plant with parallel secondary wastewater treatment train
J. Environ. Manag.
Simultaneous determination of non-steroidal anti-inflammatory drugs and oestrogenic hormones in environmental solid samples
Sci. Total Environ.
Behaviour of nonsteroidal anti-inflammatory drugs and eight of their metabolites during wastewater treatment studied by hollow fibre liquid phase microextraction and liquid chromatography mass spectrometry
Sci. Total Environ.
Occurrence, sources, and fate of pharmaceuticals in aquatic environment and soil
Environ. Pollut.
Development of a gas chromatography method for the determination of isotretinoin and its degradation products in pharmaceuticals
J. Pharmaceut. Biomed. Anal.
Sorption and degradation of wastewater-associated non-steroidal anti-inflammatory drugs and antibiotics in soils
Chemosphere
Diclofenac and its transformation products: environmental occurrence and toxicity - a review
Environ. Int.
EU-wide monitoring survey on emerging polar organic contaminants in wastewater treatment plant effluents
Water Res.
A review on the occurrence of micropollutants in the aquatic environment and their fate and removal during wastewater treatment
Sci. Total Environ.
An anionic exchange stir rod sorptive extraction based on monolithic material for the extraction of non-steroidal anti-inflammatory drugs in environmental aqueous samples
Talanta
Handbook of thin-layer chromatography
J. Chromatogr. A
Multielemental speciation analysis by advanced hyphenated technique – HPLC/ICP-MS : a review
Talanta
Analytical methods for the determination of emerging contaminants in sewage sludge samples
A review. Talanta
Thermal decomposition of energetic materials using TG-FTIR and TG-MS: a state-of-the-art review
Appl. Spectrosc. Rev.
Removal of non-steroidal anti-inflammatory drugs from aqueous environments with reusable ionic-liquid-based systems
ACS Sustain. Chem. Eng.
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This paper has been recommended for acceptance by Klaus Kümmerer.