Metabolites are overlooked in environmental risk assessments and monitoring of pharmaceuticals: The case study of pantoprazole.

The proton-pump inhibitor pantoprazole (PPZ) is one of the most consumed pharmaceuticals worldwide. Despite its high usage, reported PPZ concentrations in environmental water samples are comparatively low, which can be explained by the extensive metabolism of PPZ in the human body. Since most previous studies did not consider human PPZ metabolites it can be assumed that the current environmental exposure associated with the application of PPZ is substantially underestimated. In our study, 4'-O-demethyl-PPZ sulfide (M1) was identified as the predominant PPZ metabolite by analyzing urine of a PPZ consumer as well as the influent and effluent of a wastewater treatment plant (WWTP) using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS). M1 was found to be ubiquitously present in WWTP effluents (max. concentration: 3 000 ng/L) and surface waters in Germany. On average, the surface water concentrations of M1 were approximately 30 times higher than those of the parent compound PPZ. Laboratory scale experiments demonstrated that activated carbon can considerably adsorb M1 und thus improve its removal during wastewater and drinking water treatment. Laboratory ozonation experiments showed a fast oxidation of M1, accompanied by the formation of several ozonation products. Certain ozonation products (identities confirmed via synthesized reference standards) were also detected in water samples collected after ozonation in a full-scale WWTP. Overall lower signal intensities were observed in the effluents of a sand filter and biologically active granular activated carbon filter, suggesting that the compounds were significantly removed during these post-ozonation treatment stages.

Under the radar - Exceptionally high environmental concentrations of the high production volume chemical sulfamic acid in the urban water cycle.

Elevated concentrations of sulfamate, the anion of sulfamic acid, were found in surface waters and finished drinking water in Germany with concentrations up to 580 µg/L and 140 µg/L, respectively. Wastewater treatment plant (WWTP) effluent was identified as the dominant source of sulfamate in the urban water cycle, as sulfamate concentrations correlated positively (0.77 > r < 0.99) with concentrations of the wastewater tracer carbamazepine in samples from different waterbodies. Ozonation and activated sludge experiments proved that sulfamate can be formed from chemical and biological degradation of various precursors. Molar sulfamate yields were highly compound-specific and ranged from 2% to 56%. However, the transformation of precursors to sulfamate in WWTPs and wastewater-impacted waterbodies was found to be quantitatively irrelevant, since concentrations of sulfamate in these compartments are already high, presumably due to its primary use as an acidic cleaning agent. Sulfamate concentrations in the influent and effluent of studied WWTPs ranged from 520 µg/L to 1900 µg/L and from 490 µg/L to 1600 µg/L, respectively. Laboratory batch experiments were performed to assess the recalcitrance of sulfamate for chemical oxidation. In combination with the results from sampling conducted at full-scale waterworks, it was shown that common drinking water treatment techniques, including ozonation and filtration with activated carbon, are not capable to remove sulfamate. The results of biodegradation tests and from the analysis of samples taken at four bank filtration sites indicate that sulfamate is attenuated in the sediment/water interface of aquatic systems and during aquifer passage under aerobic and anaerobic conditions. Sulfamate concentrations decreased by between 62% and 99% during aquifer passage at the bank filtration sites. Considering the few data on short term ecotoxicity, about 30% of the presented sulfamate levels in ground and surface water samples did exceed the predicted no-effect concentration (PNEC) of sulfamate, and thus effects of sulfamate on the aquatic ecosystem of wastewater-impacted waterbodies in Germany cannot be excluded so far. Toxicological estimations suggest that no risk to human health is expected by concentrations of sulfamate typically encountered in tap water.

Trace-level determination of phosphonates in liquid and solid phase of wastewater and environmental samples by IC-ESI-MS/MS.

Phosphonates are increasingly used as water-softening agents in detergents, care products, and industrial processes. Despite poor biodegradability, high removal rates during wastewater treatment (WWT) have been observed, owing to strong adsorption affinity to activated sludge and mineral surfaces. Due to phosphonates representing challenging analytes, no method for the compound-specific quantification of phosphonates from solid samples has hitherto been published. In order to improve the data foundation on the environmental fate of phosphonates, an analytical method based on anion exchange chromatography and detection by electrospray ionization coupled to tandem mass spectrometry (IC-ESI-MS/MS) was developed, allowing the trace quantification of phosphonates from surface water (LOQs between 0.04 and 0.16 µg/L), wastewater (LOQs between 0.6 and 2.3 µg/L), sediment and suspended matter of rivers (LOQ < 0.1 mg/kg), and suspended matter of wastewater (LOQ < 1 mg/kg). Specificity and selectivity were enhanced by the implementation of isotope-labeled internal phosphonate standards derived through synthesis. This study describes the development of a comprehensive tool set for the determination of aminotris(methylenephosphonic acid) (ATMP), diethylenetriaminepenta(methylenephosphonic acid) (DTPMP), ethylenediaminetetra(methylenephosphonic acid) (EDTMP), 1-hydroxyethanediphosphonic acid (HEDP), and 2-phosphonobutane-1,2,4-tricarboxylic acid (PBTC) during WWT and in the aqueous environment. In the investigated matrices, HEDP and PBTC were generally present in highest and EDTMP in lowest abundance. The phosphonate contents detected in river water were in the sub to low µg/L range, depending on the wastewater burden, whereas contents in the low to medium µg/L range were found in untreated wastewater. The loads of the solid phases exceeded the contents of the corresponding liquid phases by roughly three orders of magnitude. Current data imply that phosphonates undergo significant partitioning to the solid phase during WWT and in natural water bodies. Graphical abstract.

Characterization of phosphonate-based antiscalants used in drinking water treatment plants by anion-exchange chromatography coupled to electrospray ionization time-of-flight mass spectrometry and inductively coupled plasma mass spectrometry.

In drinking water production, phosphonates are frequently applied as antiscalants in order to prevent the precipitation of salts on reverse osmosis membranes. Whereas the nominal constituents are defined, phosphonate-based antiscalants were found to contain significant amounts of undeclared phosphorous contaminants, particularly noticeable technical diethylenetriamine penta(methylene phosphonic acid) (DTPMP). Following a literature review on impurities of phosphonic acids, separation by anion exchange chromatography coupled with ICP-MS- and ESI-TOF-detection allowed the comprehensive characterization of technical phosphonates. After the identification of synthesis by-products, intermediates and degradation products, the quantification of the phosphorus compounds was accomplished by complementary phosphorus-sensitive ICP-MS detection. The contents of the nominal constituents as well as the organophosphorous impurities of 24 technical antiscalants were determined and compared with the manufacturer's declaration. Of all compounds detected within the technical formulations, 86% were confirmed with reference compounds. Phosphorous impurities were found to contribute to the total phosphorus content with close to 20% (in ATMP- and PBTC-based products) and 38%-65% (in DTPMP-based products). Correspondingly, the nominal compounds were found to contribute with 78%-80% (based on 6 ATMP products) and with 81.5%-83% (based on 2 PBTC products), whereas in 10 out of 12 DTPMP products the nominal compound was found to contribute with 34%-44% to the total phosphorus. Only in two products, elevated DTPMP proportions of 55% and 62% with regard to total phosphorus were determined. The screening for aminomethylphosphonic acid (AMPA) revealed contents between 1.9 mg/L and 157 mg/L. This study represents the first in-depth characterization of phosphonate-based antiscalant products and stock solutions used for drinking water production.

Emerging nitrogenous disinfection byproducts: Transformation of the antidiabetic drug metformin during chlorine disinfection of water.

As an environmental contaminant of anthropogenic origin metformin is present in the high ng/L- up to the low µg/L-range in most surface waters. Residues of metformin may lead to the formation of disinfection by-products during chlorine disinfection, when these waters are used for drinking water production. Investigations on the underlying chemical processes occurring during treatment of metformin with sodium hypochlorite in aqueous medium led to the discovery of two hitherto unknown transformation products. Both substances were isolated and characterized by HPLC-DAD, GC-MS, HPLC-ESI-TOF, (1)H-NMR and single-crystal X-ray structure determination. The immediate major chlorination product is a cyclic dehydro-1,2,4-triazole-derivate of intense yellow color (Y; C4H6ClN5). It is a solid chlorimine of limited stability. Rapid formation was observed between 10 °C and 30 °C, as well as between pH 3 and pH 11, in both ultrapure and tap water, even at trace quantities of reactants (ng/L-range for metformin, mg/L-range for free chlorine). While Y is degraded within a few hours to days in the presence of light, elevated temperature, organic solvents and matrix constituents within tap water, a secondary degradation product was discovered, which is stable and colorless (C; C4H6ClN3). This chloroorganic nitrile has a low photolysis rate in ambient day light, while being resistant to heat and not readily degraded in the presence of organic solvents or in the tap water matrix. In addition, the formation of ammonia, dimethylamine and N,N-dimethylguanidine was verified by cation exchange chromatography.