Occurrence of Antibiotics in Influent and Effluent from 3 Major Wastewater-Treatment Plants in Finland.

Wastewater-treatment plants (WWTPs) are regarded as one of the main sources of antibiotics in the environment. In the present study, the concentrations of multiple antibiotics and their metabolites belonging to 5 antibiotic classes were determined in 3 major Finnish WWTPs. An online solid phase extraction-liquid chromatography-tandem mass spectrometry method was used for the extraction and analysis of the compounds. The method was fully validated using real and synthetic wastewaters. Seven antibiotics and 3 metabolites were found in the analyzed samples. Sulfonamides were removed most efficiently, whereas macrolides usually showed negative removal efficiency during the treatment, which means that the concentrations for individual antibiotics determined in the effluent samples were higher than in the influent samples. Sulfadiazine was found at concentrations up to 1018 ng/L, which was the highest concentration of any of the detected antibiotics in influent. In the effluent samples, the highest mean concentration was found for trimethoprim (532 ng/L). The measured mass loads of the antibiotics and metabolites to the receiving waters ranged from 2 to 157 mg/d per 1000 population equivalent. The evaluated environmental risk assessment showed that clarithromycin and erythromycin might pose a risk to the environment. The present study further underlines the importance of implementing technology for efficient removal of xenobiotics during wastewater treatment. Environ Toxicol Chem 2020;39:1774-1789. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Pharmacodynamic and pharmacokinetic profile of SM-1, a triple-drug combination to increase total sleep time.

OBJECTIVE: The primary objective was to characterize the pharmacokinetics and pharmacodynamics of SM-1 after administration of a single oral dose to healthy volunteers in a placebo-controlled double-blind trial of daytime sedation. Secondary objectives were to determine the onset, duration, and offset of the sedative effects using subjective and objective measures of sedation. Safety and tolerability of SM-1 were also investigated. METHODS: Males and females 18-45 years of age received SM-1, a combination drug product comprised of diphenhydramine, zolpidem (delayed release), and lorazepam (delayed release). The pharmacokinetic profile of each drug was determined from blood samples. Sedative effects were assessed by visual analog scale, digit symbol substitution test, memory test, and quantitative electroencephalography. RESULTS: Similar number and severity of adverse events were observed following administration of SM-1 and placebo. Onset of sedation, as determined by subjective, performance, and electroencephalography measures, occurred 0.5-1 hr postdose, lasting about 7-7.5 hr. Plasma concentration curves for the two delayed-release components were altered compared with published data for unmodified drugs. Exposure values obtained with the combination product were in good agreement with published values of the drugs given individually. CONCLUSIONS: SM-1 was well tolerated and has pharmacologic activity starting within an hour of ingestion, lasting approximately 7-8 hr. Sedative activity was seen with subjective, psychomotor, and electroencephalography assays.

Slow-release L-cysteine capsule prevents gastric mucosa exposure to carcinogenic acetaldehyde: results of a randomised single-blinded, cross-over study of Helicobacter-associated atrophic gastritis.

INTRODUCTION: Helicobacter-induced atrophic gastritis with a hypochlorhydric milieu is a risk factor for gastric cancer. Microbes colonising acid-free stomach oxidise ethanol to acetaldehyde, a recognised group 1 carcinogen. OBJECTIVE: To assess gastric production of acetaldehyde and its inert condensation product, non-toxic 2-methyl-1,3-thiazolidine-4-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine or placebo. METHODS: Seven patients with biopsy-confirmed atrophic gastritis, low serum pepsinogen and high gastrin-17 were studied in a cross-over single-blinded design. On separate days, patients randomly received 200 mg slow-release L-cysteine or placebo with intragastric instillation of 15% (0.3 g/kg) ethanol. After intake, gastric concentrations of ethanol, acetaldehyde, L-cysteine and MTCA were analysed. RESULTS: Administration of L-cysteine increased MTCA (p < .0004) and decreased gastric acetaldehyde concentrations by 68% (p < .0001). The peak L-cysteine level was 7552 ± 2687 µmol/L at 40 min and peak MTCA level 196 ± 98 µmol/L at 80 min after intake. Gastric L-cysteine and MTCA concentrations were maintained for 3 h. The AUC for MTCA was 11-fold higher than acetaldehyde, indicating gastric first-pass metabolism of ethanol. With placebo, acetaldehyde remained elevated also at low ethanol concentrations representing 'non-alcoholic' beverages and food items. CONCLUSIONS: After gastric ethanol instillation, slow-release L-cysteine eliminates acetaldehyde to form inactive MTCA, which remains in gastric juice for up to 3 h. High acetaldehyde levels indicate a marked gastric first-pass metabolism of ethanol resulting in gastric accumulation of carcinogenic acetaldehyde. Local exposure of the gastric mucosa to acetaldehyde can be mitigated by slow-release L-cysteine capsules.

Seasonal variation of pharmaceutical concentrations in a river/lake system in Eastern Finland.

In this study, the concentrations of 15 pharmaceuticals were monitored during four seasons (February, May, July, and November 2010) along a 32 km stretch of a highly wastewater polluted watercourse (River Rakkolanjoki, Lake Haapajärvi) in Eastern Finland. The aim was to study the seasonal variation in the elimination of the pharmaceuticals and the stability of the compounds along the watercourse. The analysis was carried out using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method combined with extraction and preconcentration on HLB solid phase extraction (SPE) cartridges. Pharmaceutical concentrations were determined at 9 points along the watercourse, and loads and removal of parent compounds were calculated using flow data from the discharge point and the last sampling point. The pharmaceuticals were found in concentrations ranging from low ng l(-1) to low µg l(-1) values at the discharge point and at concentrations of 0-556 ng l(-1) at the last sampling point. The rate of elimination of the pharmaceutical load was significantly higher in May and July than in February and November. There were clear differences in the stability of the individual compounds along the watercourse. Carbamazepine was not eliminated during any season, while ibuprofen, ketoprofen and sertraline were fully eliminated over the studied stretch of river during the summer months. Other compounds showed continuous elimination independent of the season, indicating different elimination paths, such as sorption, biodegradation and phototransformation, for the studied compounds.

Analysis of dye degradation products and assessment of the dye purity in dye-sensitized solar cells.

RATIONALE: For commercialization of dye-sensitized solar cells (DSSCs), improvement of their long-term stability and efficiency is important. A key component in solar cells is the dye, its high purity and high stability. Here, methods for dye extraction and purification, and for determination of dye purity and dye degradation in DSSCs, were developed. METHODS: A method was developed for extraction of the dye Z907 from intact solar cells using a water/ethanol mixture containing tetrabutylammonium hydroxide. The N719 dye synthesized in our laboratory was purified by gel filtration on Sephadex LH20. These dyes, along with the dyes N3 and RuL2 (NC)2, were analyzed using nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography coupled to an electrospray ionization quadrupole-time-of-flight mass analyzer (LC/MS) operating in negative ionization mode. RESULTS: Purification of the synthesized N719 removed several impurities, including its undesired isomer with the thiocyanate ligand attached to ruthenium through sulfur instead of nitrogen. The dyes N719 and Z907 were successfully extracted from solar cells and together with N3 and RuL2 (NC)2 analyzed by LC/MS, although N719 isomerized almost immediately in basic aqueous solution. The [M-H](-1) ions were observed and the measured mass was within a ±6 ppm range from the exact mass. CONCLUSIONS: LC/MS in combination with NMR spectroscopy was shown to provide useful information on dye structure, purity, and on the efficiency of the purification methods. These methods allow for further studies of solar cell dyes, which may provide the detailed information needed for the improvement and eventual commercialization of the solar cell technology.

The mussel caging approach in assessing biological effects of wastewater treatment plant discharges in the Gulf of Finland (Baltic Sea).

Biological effects of wastewater treatment plant (WWTP) effluents were investigated in Baltic mussels (Mytilus trossulus) caged for one month 800m and 1100m from the WWTP discharge site and at a reference site 4km away. Significant antioxidant, genotoxic and lysosomal responses were observed close to the point of the WWTP discharge. Passive samplers (POCIS) attached to the cages indicated markedly higher water concentrations of various pharmaceuticals at the two most impacted sites. Modeling the dispersal of a hypothetical passive tracer compound from the WWTP discharge site revealed differing frequencies and timing of the exposure periods at different caging sites. The study demonstrated for the first time the effectiveness of the mussel caging approach in combination with passive samplers and the application of passive tracer modeling to examine the true exposure patterns at point source sites such as WWTP pipe discharges in the Baltic Sea.

Spatial differences and temporal changes in illicit drug use in Europe quantified by wastewater analysis.

AIMS: To perform wastewater analyses to assess spatial differences and temporal changes of illicit drug use in a large European population. DESIGN: Analyses of raw wastewater over a 1-week period in 2012 and 2013. SETTING AND PARTICIPANTS: Catchment areas of wastewater treatment plants (WWTPs) across Europe, as follows: 2012: 25 WWTPs in 11 countries (23 cities, total population 11.50 million); 2013: 47 WWTPs in 21 countries (42 cities, total population 24.74 million). MEASUREMENTS: Excretion products of five illicit drugs (cocaine, amphetamine, ecstasy, methamphetamine, cannabis) were quantified in wastewater samples using methods based on liquid chromatography coupled to mass spectrometry. FINDINGS: Spatial differences were assessed and confirmed to vary greatly across European metropolitan areas. In general, results were in agreement with traditional surveillance data, where available. While temporal changes were substantial in individual cities and years (P ranging from insignificant to <10(-3) ), overall means were relatively stable. The overall mean of methamphetamine was an exception (apparent decline in 2012), as it was influenced mainly by four cities. CONCLUSIONS: Wastewater analysis performed across Europe provides complementary evidence on illicit drug consumption and generally concurs with traditional surveillance data. Wastewater analysis can measure total illicit drug use more quickly and regularly than is the current norm for national surveys, and creates estimates where such data does not exist.

The anti-inflammatory drugs diclofenac, naproxen and ibuprofen are found in the bile of wild fish caught downstream of a wastewater treatment plant.

Pharmaceutical residues are ubiquitous in rivers, lakes, and at coastal waters affected by discharges from municipal wastewater treatment plants. In this study, the presence of 17 different pharmaceuticals and six different phase I metabolites was determined in the bile of two wild fish species, bream (Abramis brama) and roach (Rutilus rutilus). The fish were caught from a lake that receives treated municipal wastewater via a small river. Prior to analyses, the bile content was enzymatically hydrolyzed to convert the glucuronide metabolites into the original pharmaceuticals or phase I metabolites. The solid phase extracts of hydrolyzates were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the multiple reaction monitoring mode. The anti-inflammatory drug naproxen could be detected in all the six bream and roach bile samples. Diclofenac was found in five of the bream and roach samples, while ibuprofen was detected in three bream and two roach samples. The observed bile concentrations of diclofenac, naproxen, and ibuprofen in bream ranged from 6 to 95 ng mL(-1), 6 to 32 ng mL(-1), and 16 to 34 ng mL(-1), respectively. The corresponding values in roach samples ranged from 44 to 148 ng mL(-1), 11 to 103 ng mL(-1) and 15 to 26 ng mL(-1), respectively. None of the other studied compounds could be detected. The study shows that pharmaceuticals originating from wastewater treatment plant effluents can be traced to the bile of wild bream and roach living in a lake where diclofenac, naproxen, and ibuprofen are present as pollutants.

Comparing illicit drug use in 19 European cities through sewage analysis.

The analysis of sewage for urinary biomarkers of illicit drugs is a promising and complementary approach for estimating the use of these substances in the general population. For the first time, this approach was simultaneously applied in 19 European cities, making it possible to directly compare illicit drug loads in Europe over a 1-week period. An inter-laboratory comparison study was performed to evaluate the analytical performance of the participating laboratories. Raw 24-hour composite sewage samples were collected from 19 European cities during a single week in March 2011 and analyzed for the urinary biomarkers of cocaine, amphetamine, ecstasy, methamphetamine and cannabis using in-house optimized and validated analytical methods. The load of each substance used in each city was back-calculated from the measured concentrations. The data show distinct temporal and spatial patterns in drug use across Europe. Cocaine use was higher in Western and Central Europe and lower in Northern and Eastern Europe. The extrapolated total daily use of cocaine in Europe during the study period was equivalent to 356 kg/day. High per capita ecstasy loads were observed in Dutch cities, as well as in Antwerp and London. In general, cocaine and ecstasy loads were significantly elevated during the weekend compared to weekdays. Per-capita loads of methamphetamine were highest in Helsinki and Turku, Oslo and Budweis, while the per capita loads of cannabis were similar throughout Europe. This study shows that a standardized analysis for illicit drug urinary biomarkers in sewage can be applied to estimate and compare the use of these substances at local and international scales. This approach has the potential to deliver important information on drug markets (supply indicator).

Reed beds may facilitate transfer of tributyltin from aquatic to terrestrial ecosystems through insect vectors in the Archipelago Sea, SW Finland.

Due to their adsorptive behavior, organotin compounds (OTCs), such as tributyltin (TBT), are accumulated in aquatic sediments. They resist biodegradation and, despite a ban in 2008, are a potential source for future exposure. Sediment OTCs have mostly been measured from sites of known high concentrations such as ports, shipping lanes, and marine dredging waste sites. The possible flow of OTCs from marine to terrestrial ecosystems, however, has not been studied. In the present study, the authors assessed whether sediments in common reed beds (Phragmites australis) accumulate TBT and whether chironomid (Diptera: Chironomidae) communities developing in reed-bed sediments act as vectors in the transfer of TBT from aquatic to terrestrial ecosystems in the Airisto channel, Archipelago Sea. The authors also investigated whether distance from the only known source and depth and TBT concentration of the adjacent shipping lane affect reed-bed concentrations. Thirty-six sites along the Airisto channel were sampled at 2-km intervals with triplicate samples from reed beds and the adjacent shipping lane for sediment and seven reed-bed sites for chironomids, and these were analyzed with an solid phase extraction liquid chromatography tamdem mass spectrometry method. The closer to the source the sample site was, the higher the measured TBT concentrations were; and the deeper the shipping lane, the lower the concentration of TBT in reed-bed sediments. The chironomid TBT concentrations correlated with reed-bed sediment TBT concentrations and showed evidence of accumulation. Therefore, TBT may be transferred, through the food web, from aquatic to terrestrial ecosystems relatively close to a source through ecosystem boundaries, such as common reed beds, which are areas of high insect biomass production in the Archipelago Sea.

Inkjet printing of drug substances and use of porous substrates-towards individualized dosing.

Medicines are most often oral solid dosage forms made into tablets or capsules, and there is little room for individualized doses. The drug substance and additives are processed through multiple production phases, including complex powder handling steps. In drug manufacturing, the control of the solid-state properties of active pharmaceutical ingredient (API) is essential and it offers opportunities for enhancement of drug delivery systems. In this context, inkjet printing technologies have emerged over the last decades in pharmaceutical and biological applications and offer solutions for controlling material and product characteristics with high precision. Here we report the concept of conventional inkjet printing technology to produce printable pharmaceutical dosage forms on porous substrates. Data are shown to demonstrate inkjet printing of APIs into paper substrates, and how the model drug substances (paracetamol, theophylline, and caffeine) are penetrating the porous substrates used. The method enables controlling not only the deposition but also the crystallization of the drug substances. We anticipate that the inkjet printing approach has immense potential in making sophisticated drug delivery systems by use of porous substrates in the future. For example, it may offer new perspectives for solving problems around poorly soluble drugs and dosing low-dose medicines accurately. Furthermore, with the advent of genetic mapping of humans, controlled inkjet dosing can bring solutions to fabricate on-demand individualized medicines for patients.