Occurrence of Z-drugs, benzodiazepines, and ketamine in wastewater in the United States and Mexico during the Covid-19 pandemic.

Z-drugs, benzodiazepines and ketamine are classes of psychotropic drugs prescribed for treating anxiety, sleep disorders and depression with known side effects including an elevated risk of addiction and substance misuse. These drugs have a strong potential for misuse, which has escalated over the years and was hypothesized here to have been exacerbated during the COVID-19 pandemic. Wastewater-based epidemiology (WBE) constitutes a fast, easy, and relatively inexpensive approach to epidemiological surveys for understanding the incidence and frequency of uses of these drugs. In this study, we analyzed wastewater (n = 376) from 50 cities across the United States and Mexico from July to October 2020 to estimate drug use rates during a pandemic event. Both time and flow proportional composite and grab samples of untreated municipal wastewater were analyzed using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry to determine loadings of alprazolam, clonazepam, diazepam, ketamine, lorazepam, nordiazepam, temazepam, zolpidem, and zaleplon in raw wastewater. Simultaneously, prescription data of the aforementioned drugs were extracted from the Medicaid database from 2019 to 2021. Results showed high detection frequencies of ketamine (90 %), lorazepam (87 %), clonazepam (76 %) and temazepam (73 %) across both Mexico and United States and comparatively lower detection frequencies for zaleplon (22 %), zolpidem (9 %), nordiazepam (<1 %), diazepam (<1 %), and alprazolam (<1 %) during the pandemic. Average mass consumption rates, estimated using WBE and reported in units of mg/day/1000 persons, ranged between 62 (temazepam) and 1100 (clonazepam) in the United States. Results obtained from the Medicaid database also showed a significant change (p < 0.05) in the prescription volume between the first quarter of 2019 (before the pandemic) and the first quarter of 2021 (pandemic event) for alprazolam, clonazepam and lorazepam. Study results include the first detections of zaleplon and zolpidem in wastewater from North America.

Quantitative Determination and Environmental Risk Assessment of 102 Chemicals of Emerging Concern in Wastewater-Impacted Rivers Using Rapid Direct-Injection Liquid Chromatography-Tandem Mass Spectrometry.

The rapid source identification and environmental risk assessment (ERA) of hundreds of chemicals of emerging concern (CECs) in river water represent a significant analytical challenge. Herein, a potential solution involving a rapid direct-injection liquid chromatography-tandem mass spectrometry method for the quantitative determination of 102 CECs (151 qualitatively) in river water is presented and applied across six rivers in Germany and Switzerland at high spatial resolution. The method required an injection volume of only 10 µL of filtered sample, with a runtime of 5.5 min including re-equilibration with >10 datapoints per peak per transition (mostly 2 per compound), and 36 stable isotope-labelled standards. Performance was excellent from the low ng/L to µg/L concentration level, with 260 injections possible in any 24 h period. The method was applied in three separate campaigns focusing on the ERA of rivers impacted by wastewater effluent discharges (1 urban area in the Basel city region with 4 rivers, as well as 1 semi-rural and 1 rural area, each focusing on 1 river). Between 25 and 40 compounds were quantified directly in each campaign, and in all cases small tributary rivers showed higher CEC concentrations (e.g., up to ~4000 ng/L in total in the R. Schwarzach, Bavaria, Germany). The source of selected CECs could also be identified and differentiated from other sources at pre- and post- wastewater treatment plant effluent discharge points, as well as the effect of dilution downstream, which occurred over very short distances in all cases. Lastly, ERA for 41 CECs was performed at specific impacted sites, with risk quotients (RQs) at 1 or more sites estimated as high risk (RQ > 10) for 1 pharmaceutical (diclofenac), medium risk (RQ of 1-10) for 3 CECs (carbamazepine, venlafaxine, and sulfamethoxazole), and low risk (RQ = 0.1-1.0) for 7 CECs (i.e., RQ > 0.1 for 11 CECs in total). The application of high-throughput methods like this could enable a better understanding of the risks of CECs, especially in low flow/volume tributary rivers at scale and with high resolution.

Multicompartment and cross-species monitoring of contaminants of emerging concern in an estuarine habitat.

The fate of many chemicals in the environment, particularly contaminants of emerging concern (CEC), have been characterised to a limited extent with a major focus on occurrence in water. This study presents the characterisation, distribution and fate of multiple chemicals including pharmaceuticals, recreational drugs and pesticides in surface water, sediment and fauna representing different food web endpoints in a typical UK estuary (River Colne, Essex, UK). A comparison of contaminant occurrence across different benthic macroinvertebrates was made at three sites and included two amphipods (Gammarus pulex &Crangon crangon), a polychaete worm (Hediste diversicolor) and a gastropod (Peringia ulvae). Overall, multiple contaminants were determined in all compartments and ranged from;

High-throughput multi-residue quantification of contaminants of emerging concern in wastewaters enabled using direct injection liquid chromatography-tandem mass spectrometry.

A rapid quantitative method for 135 contaminants of emerging concern (CECs) in untreated wastewater enabled with direct injection liquid chromatography-tandem mass spectrometry is presented. All compounds were analysed within 5 min on a short biphenyl cartridge using only 10 µL of filtered sample per injection. Up to 76 compounds were monitored simultaneously during the gradient (including mostly two transitions per compound and stable isotope-labelled analogues) while yielding >10 data points per peak. Evaluation of seven solid phase extraction sorbents showed no advantage for wastewater matrix removal. Excellent linearity, range, accuracy and precision was achieved for most compounds. Matrix effects were <11 % and detection limits were <30 ng L-1 on average. Application to untreated wastewater samples from three wastewater treatment works in the UK, USA and Mexico, enabled quantification of 56 compounds. Banned and EU 'watch-list' substances are critically discussed, including pesticides, macrolide antibiotics, diclofenac, illicit drugs as well as multiple pharmaceuticals and biocides. This high-throughput method sets a new standard for the speedy and confident determination of over a hundred CECs in wastewater at the part-per-trillion level, as demonstrated by performing over 260 injections per day.

Synthesis and Antimicrobial Activity of Phosphonopeptide Derivatives Incorporating Single and Dual Inhibitors.

In diagnostic microbiology, culture media are widely used for detection of pathogenic bacteria. Such media employ various ingredients to optimize detection of specific pathogens such as chromogenic enzyme substrates and selective inhibitors to reduce the presence of commensal bacteria. Despite this, it is rarely possible to inhibit the growth of all commensal bacteria, and thus pathogens can be overgrown and remain undetected. One approach to attempt to remedy this is the use of "suicide substrates" that can target specific bacterial enzymes and selectively inhibit unwanted bacterial species. With the purpose of identifying novel selective inhibitors, six novel phosphonopeptide derivatives based on d/l-fosfalin and ß-chloro-l-alanine were synthesized and tested on 19 different strains of clinically relevant bacteria. Several compounds show potential as useful selective agents that could be exploited in the recovery of several bacterial pathogens including Salmonella, Pseudomonas aeruginosa, and Listeria.

Biomonitoring of pesticides, pharmaceuticals and illicit drugs in a freshwater invertebrate to estimate toxic or effect pressure.

Multiple classes of environmental contaminants have been found in aquatic environments, globally. Understanding internalised concentrations in the organism could further improve the risk assessment process. The present study is concerned with the determination of several contaminant classes (107 compounds) in Gammarus pulex collected from 15 sites covering 5 river catchments across Suffolk, UK. Quantitative method performance was acceptable for 67 compounds including pharmaceuticals, pesticides, illicit drugs and drugs of abuse. A total of 56 compounds were detectable and ranged from