Removal efficiency for emerging contaminants in a WWTP from Madrid (Spain) after secondary and tertiary treatment and environmental impact on the Manzanares River

The effluents from wastewater treatment plants (WWTPs) can be an important contamination source for receiving waters. In this work, a comprehensive study on the impact of a WWTP from Madrid on the aquatic environment has been performed, including a wide number of pharmaceuticals and pesticides, among them those included in the European Watch List. 24-h composite samples of influent (IWW) and effluent wastewater after secondary (EWW2) and after secondary + tertiary treatment (EWW3) were monitored along two campaigns. Average weekly concentrations in IWW and EWW2 and EWW3 allowed estimating the removal efficiency of the WWTP for pharmaceutical active substances (PhACs). In addition, the impact of EWW3 on the water quality of the Manzanares River was assessed, in terms of PhAC and pesticide concentrations, through analysis of the river water collected upstream and downstream of the discharge point. After a preliminary risk assessment, a detailed evaluation of the impact on the aquatic environment, including a toxicological study and screening of pharmaceutical metabolites, was made for the seven most relevant PhACs: sulfamethoxazole, azithromycin and clarithromycin (antibiotics), metoprolol (antihypertensive), diclofenac (anti-inflammatory/analgesic), irbesartan (antihypertensive), and the antidepressant venlafaxine. Among selected PhACs, irbesartan, clarithromycin and venlafaxine presented moderate or high risk in the river water downstream of the discharge. Albeit no acute toxicity was detected, more detailed studies should be carried out for these substances, including additional toxicological studies, to set up potential sublethal and chronic effects on aquatic organisms.This work was developed under the financial support of DRACE INFRAESTRUCTURAS S.A. as a part of the project Estudio de contaminantes emergentes en aguas residuales y superficiales de Madrid. The authors acknowledge the support of Jose Ramon Rodriguez from DRACE INFRAESTRUCTURAS S.A., for collection of wastewater and surface water samples, as well as the discussion and useful suggestions from Jesus Angel López, Pedro Miguel Catalinas and Maria Elvira Benito, from Sub-Direccion General de Aguas, Ayuntamiento de Madrid. The University Jaume I of Castellón, Spain (project UJI-B2018-55), the Ministry of Science, Innovation and University, Spain (Ref RTI2018-097417-B-I00) and Generalitat Valenciana, Spain (research group of excellence PROMETEO 2019/040) are also acknowledged. The authors are very grateful to the Serveis Centrals d'Instrumentació Científica (SCIC) of University Jaume I for the use of LC-MS/MS instrumentation

The search for the 'next' euphoric non-fentanil novel synthetic opioids on the illicit drugs market: current status and horizon scanning

Purpose: A detailed review on the chemistry and pharmacology of non-fentanil novel synthetic opioid receptor agonists, particularly N-substituted benzamides and acetamides (known colloquially as U-drugs) and 4-aminocyclohexanols, developed at the Upjohn Company in the 1970s and 1980s is presentedMethod: Peer-reviewed literature, patents, professional literature, data from international early warning systems and drug user fora discussion threads have been used to track their emergence as substances of abuse.Results: In terms of impact on drug markets, prevalence and harm, the most significant compound of this class to date has been U-47700 (trans-3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide), reported by users to give short-lasting euphoric effects and a desire to re-dose. Since U-47700 was internationally controlled in 2017, a range of related compounds with similar chemical structures, adapted from the original patented compounds, have appeared on the illicit drugs market. Interest in a structurally unrelated opioid developed by the Upjohn Company and now known as BDPC/bromadol appears to be increasing and should be closely monitored.Conclusions: International early warning systems are an essential part of tracking emerging psychoactive substances and allow responsive action to be taken to facilitate the gathering of relevant data for detailed risk assessments. Pre-emptive research on the most likely compounds to emerge next, so providing drug metabolism and pharmacokinetic data to ensure that new substances are detected early in toxicological samples is recommended. As these compounds are chiral compounds and stereochemistry has a large effect on their potency, it is recommended that detection methods consider the determination of configuration

Electrochemical oxidation of meglumine in a pharmaceutical formulation using a nanocomposite anode

The electrocatalytic oxidation of meglumine and gadoterate meglumine (Gd-DOTA) on a TiO2-Ni(SO4)0.3(OH)1.4 composite anode was investigated in alkaline medium (5 M KOH) using cyclic voltammetry and chronoamperometry. The composite was prepared by hydrothermal method and the morphology and structure of the produced nanoparticles were studied by scanning electron microscopy with energy-dispersive X-ray spectroscopy, X-ray diffraction, atomic force microscopy, BET surface area analysis and Fourier transform infrared spectroscopy. The characterization revealed the formation of Ni(SO4)0.3(OH)1.4 nanobelts dispersed on TiO2 nanoaggregates. The composite was coated onto a porous graphite rod, showing good adherence without requiring any binder (according to their anodic and cathodic charges). The supported composite was electrocatalytic, allowing the oxidation of meglumine, either as pure reagent or contained in gadoterate meglumine solutions. Electrochemical methods allowed determining the kinetic parameters, such as the electron transfer coefficient α, the total number of electrons n and the standard heterogeneous rate constant k0 for the reaction of meglumine. The chronoamperometric tests informed about the good stability of the composite anode upon meglumine oxidation at +0.6 V for 10 h. The electrochemical oxidation of meglumine in a commercial pharmaceutical formulation (Dotarem®) was corroborated via ultra-high performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry