Pharmacologically active compounds in the environment and their chirality

Pharmacologically active compounds including both legally used pharmaceuticals and illicit drugs are potent environmental contaminants. Extensive research has been undertaken over the recent years to understand their environmental fate and toxicity. The one very important phenomenon that has been overlooked by environmental researchers studying the fate of pharmacologically active compounds in the environment is their chirality. Chiral drugs can exist in the form of enantiomers, which have similar physicochemical properties but differ in their biological properties such as distribution, metabolism and excretion, as these processes (due to stereospecific interactions of enantiomers with biological systems) usually favour one enantiomer over the other. Additionally, due to different pharmacological activity, enantiomers of chiral drugs can differ in toxicity. Furthermore, degradation of chiral drugs during wastewater treatment and in the environment can be stereoselective and can lead to chiral products of varied toxicity. The distribution of different enantiomers of the same chiral drug in the aquatic environment and biota can also be stereoselective. Biological processes can lead to stereoselective enrichment or depletion of the enantiomeric composition of chiral drugs. As a result the very same drug might reveal different activity and toxicity and this will depend on its origin and exposure to several factors governing its fate in the environment. In this critical review a discussion of the importance of chirality of pharmacologically active compounds in the environmental context is undertaken and suggestions for directions in further research are made. Several groups of chiral drugs of major environmental relevance are discussed and their pharmacological action and disposition in the body is also outlined as it is a key factor in developing a full understanding of their environmental occurrence, fate and toxicity. This review will be of interest to environmental scientists, especially those interested in issues associated with environmental contamination with pharmacologically active compounds and chiral pollutants. As the review will outline current state of knowledge on chiral drugs, it will be of value to anyone interested in the phenomenon of chirality, chiral drugs, their stereoselective disposition in the body and environmental fat

A review on emerging contaminants in wastewaters and the environment: current knowledge, understudied areas and recommendations for future monitoring.

This review identifies understudied areas of emerging contaminant (EC) research in wastewaters and the environment, and recommends direction for future monitoring. Non-regulated trace organic ECs including pharmaceuticals, illicit drugs and personal care products are focused on due to ongoing policy initiatives and the expectant broadening of environmental legislation. These ECs are ubiquitous in the aquatic environment, mainly derived from the discharge of municipal wastewater effluents. Their presence is of concern due to the possible ecological impact (e.g., endocrine disruption) to biota within the environment. To better understand their fate in wastewaters and in the environment, a standardised approach to sampling is needed. This ensures representative data is attained and facilitates a better understanding of spatial and temporal trends of EC occurrence. During wastewater treatment, there is a lack of suspended particulate matter analysis due to further preparation requirements and a lack of good analytical approaches. This results in the under-reporting of several ECs entering wastewater treatment works (WwTWs) and the aquatic environment. Also, sludge can act as a concentrating medium for some chemicals during wastewater treatment. The majority of treated sludge is applied directly to agricultural land without analysis for ECs. As a result there is a paucity of information on the fate of ECs in soils and consequently, there has been no driver to investigate the toxicity to exposed terrestrial organisms. Therefore a more holistic approach to environmental monitoring is required, such that the fate and impact of ECs in all exposed environmental compartments are studied. The traditional analytical approach of applying targeted screening with low resolution mass spectrometry (e.g., triple quadrupoles) results in numerous chemicals such as transformation products going undetected. These can exhibit similar toxicity to the parent EC, demonstrating the necessity of using an integrated analytical approach which compliments targeted and non-targeted screening with biological assays to measure ecological impact. With respect to current toxicity testing protocols, failure to consider the enantiomeric distribution of chiral compounds found in the environment, and the possible toxicological differences between enantiomers is concerning. Such information is essential for the development of more accurate environmental risk assessment

Community sewage sensors towards evaluation of drug use trends: detection of cocaine in wastewater with DNA-directed immobilization aptamer sensors

Illicit drug use has a global concern and effective monitoring and interventions are highly required to combat drug abuse. Wastewater-based epidemiology (WBE) is an innovative and cost-effective approach to evaluate community-wide drug use trends, compared to traditional population surveys. Here we report for the first time, a novel quantitative community sewage sensor (namely DNA-directed immobilization of aptamer sensors, DDIAS) for rapid and cost-effective estimation of cocaine use trends via WBE. Thiolated single-stranded DNA (ssDNA) probe was hybridized with aptamer ssDNA in solution, followed by co-immobilization with 6-mercapto-hexane onto the gold electrodes to control the surface density to effectively bind with cocaine. DDIAS was optimized to detect cocaine at as low as 10 nM with a dynamic range from 10 nM to 5 μM, which were further employed for the quantification of cocaine in wastewater samples collected from a wastewater treatment plant in seven consecutive days. The concentration pattern of the sampling week is comparable with that from mass spectrometry. Our results demonstrate that the developed DDIAS can be used as community sewage sensors for rapid and cost-effective evaluation of drug use trends, and potentially implemented as a powerful tool for on-site and real-time monitoring of wastewater by un-skilled personnel

Monitoring genetic population biomarkers for wastewater-based epidemiology

We report a rapid “sample-to-answer” platform that can be used for the quantitative monitoring of genetic biomarkers within communities through the analysis of wastewater. The assay is based on the loop-mediated isothermal amplification (LAMP) of nucleic acid biomarkers and shows for the first time the ability to rapidly quantify human-specific mitochondrial DNA (mtDNA) from raw untreated wastewater samples. mtDNA provides a model population biomarker associated with carcinogenesis including breast, renal and gastric cancers. To enable a sample-to-answer, field-based technology, we integrated a filter to remove solid impurities and perform DNA extraction and enrichment into a low cost lateral flow-based test. We demonstrated mtDNA detection over seven consecutive days, achieving a limit of detection of 40 copies of human genomic DNA per reaction volume. The assay can be performed at the site of sample collection, with minimal user intervention, yielding results within 45 min and providing a method to monitor public health from wastewater

Multi-residue analysis of 90 emerging contaminants in liquid and solid environmental matrices by ultra-high-performance liquid chromatography tandem mass spectrometry.

Reported here in is new analytical methodology for the determination of 90 emerging contaminants (ECs)in liquid environmental matrices (crude wastewater, final effluent and river water). The application of a novel buffer, ammonium fluoride improved signal response for several ECs determined in negative ionisation mode. Most notably the sensitivity of steroid estrogens was improved by 4–5 times in environmental extracts. Method recoveries ranged from 40 to 152% in all matrices and method quantitation limits (MQLs) achieved were [less than]1 ng L−1for numerous ECs. Development of a microwave assisted extraction(MAE) protocol as an additional sample extraction step for solid matrices enabled 63 ECs to be simultaneously analysed in digested sludge. To the authors knowledge this is considerably more than any previously reported MAE method. Here, MQLs ranged from 0.1–24.1 ng g−1dry weight. The application of MAE offers several advantages over pressurized liquid extraction including faster sample preparation, lower solvent requirements, and the ability to perform several extractions simultaneously as well as lower purchasing and running costs. To demonstrate the method’s sensitivity, application to environmental samples revealed 68 and 40 ECs to be above their respective MQL in liquid environmental samples and digested sludge, respectively. To date, this is the most comprehensive multi-residue analytical method reported in the literature for the determination of ECs in both liquid and solid environmental matrices

Catalytic ozonation of chlorinated VOCs on ZSM-5 zeolites and alumina:formation of chlorides

This study aims to understand the mechanisms and kinetics of chlorinated volatile organic chemicals (VOCs) removal during the catalytic ozonation process on γ-alumina and ZSM-5 zeolites. Both the H-ZSM-5 and Na-ZSM-5 types with different SiO2/Al2O3 ratios and counter ions (Z1000H:SiO2/Al2O3 = 1000, Z900Na:SiO2/Al2O3 = 900, Z25H:SiO2/Al2O3 = 25 and Z25Na:SiO2/Al2O3 = 25) were studied. In order to fully understand the mechanisms behind the catalytic processes, degradation of VOCs and chlorides formation were investigated during both ozonation alone and catalytic ozonation on alumina and zeolites. The effects of pH and hydroxyl radical scavengers on the efficiency of catalytic ozonation on alumina and zeolites were also studied. The results revealed that, as opposed to alumina, zeolites promoted decomposition of VOCs. Furthermore, the decomposition of chlorinated VOCs resulted in the generation of chlorides at significantly higher levels when compared with ozonation alone. The presence of hydroxyl radical scavengers had no significant effect on the removal rates of VOCs and the generation of chlorides in the presence of zeolites. It is therefore suggested that catalytic ozonation of organic VOCs on zeolites proceeds via a non-radical mechanism that involves reactions of molecular ozone with pollutants adsorbed on the surface of zeolites.</p

New framework to diagnose the direct disposal of prescribed drugs in wastewater: a case study of the antidepressant fluoxetine.

Intentional or accidental release (direct disposal) of high loads of unused pharmaceuticals into wastewater can go unnoticed. Here, direct disposal of a pharmaceutical drug via the sewer network was identified for the first time using wastewater analysis. An irregularly high load of the antidepressant fluoxetine in raw wastewater (10.5 ± 2.4 g d–1) was up to 11 times greater than any other day. National prescription data revealed a predicted daily fluoxetine load for the studied treatment works to be 0.4–1.6 g d–1. Enantio-selective analysis showed the high load of fluoxetine was present as a racemic mixture, which is typical for fluoxetine in dispensed formulations. As fluoxetine undergoes stereoselective metabolism within the body, a racemic mixture in wastewater suggests a nonconsumed drug was the major contributor of the high load. This was confirmed by its major metabolite norfluoxetine whose load did not increase on this day. Considering the most commonly prescribed formulation of fluoxetine, this increased load accounts for the disposal of ~915 capsules. Furthermore, as fluoxetine is prescribed as one capsule per day, disposal is unlikely to be at the patient level. It is postulated that direct disposal was from a facility which handles larger quantities of the drug (e.g., a pharmacy)

Occurrence of pharmaceutical residues, personal care products, lifestyle chemicals, illicit drugs and metabolites in wastewater and receiving surface waters of Krakow agglomeration in South Poland

This is the first study of broad range of chemical classes CECs conducted in the upper Wisla river catchment including the biggest WWTPs in this region and surface waters. The list of compounds is extensive and the paper provides, for the first time, better understanding of environmental burden from PCPCs in Poland. Cumulative contribution of hypertension pharmaceuticals, nonsteroidal anti-inflammatory drugs (NSAIDs) and lifestyle chemicals was 89% and 95% in wastewater influent, and 75% in wastewater effluent at both WWTPs. Significant removal efficiencies, exceeding 90%, were found for parabens, UV filters, NSAIDs, steroid estrogens, plasticizers, antibacterials/antibiotics, stimulants and metabolites and lifestyle chemicals. The comparison of the average mass loads of CECs between the influent and effluent, has shown that 27% and 29% of all detected CECs were removed by less than 50%. An increase of concentrations of CECs in the effluent was observed for 18% and 20% of all detected CECs in Kujawy and Plaszow WWTPs, respectively. Negative mass balances of fexofenadine, venlafaxine, o-desmethyltramadol, ketamine and temazepam were noted within WWTPs, which are a result of dissolution of persistent contaminants accumulated in aggregates and/or back-transformation or de-conjugation of metabolites into parent compounds. 44 CECs were detected in surface waters located upstream and downstream of the WWTPs. The concentrations of compounds were largely dependent on the dilution factor of WWTP discharge. The risk quotation (RQ) values for compounds present in surface waters were calculated in relation to their potential for bioaccumulation. Among compounds with high potential for bioaccumulation, with log KOW ≥ 4.5, diclofenac, atorvastatin and triclosan were found to be of high risk. Many CECs with high, moderate or even low environmental impact have shown high potential for bioaccumulation and should be considered as priority at the same risk level. Moreover, possible synergistic action is still of concern