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Ibuprofen (IBU) and diclofenac (DCF) are non-steroidal anti-inflammatory pharmaceuticals. They are frequently detected in wastewater and in the environment. Due to their harmful effect on aquatic o...

Carbamazepine (CBZ) is a recalcitrant pharmaceutical often detected in wastewater and in the environment. CBZ can be removed from wastewater through advanced oxidation treatment methods such as ozonation. In this study, CBZ and its transformation product 1-(2-benzaldehyde)-(1H,3H)-quinazoline-2,4-dione (BQD) were ozonated, and the formation and transformation of their ozonation products were investigated using liquid chromatography coupled to ion trap mass spectrometry and high-resolution mass spectrometry as well as nuclear magnetic resonance (NMR). The main products, 1-(2-benzaldehyde)-4-hydro-(1H,3H)-quinazoline-2-one (BQM) and BQD were quantified using isolated standards and LC-UV. Of the original CBZ concentration, 74% was transformed into BQM and 83% of BQM was further transformed into BQD. Both products are more stable than CBZ and could still be detected after 240 min of ozonation. Another major product, 2,2′-azanediyldibenzaldehyde (TP225) was for the first time identified using NMR. Twelve further CBZ products were identified. Electronic supplementary material The online version of this article (10.1007/s11356-020-08795-0) contains supplementary material, which is available to authorized users.

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.

Aqueous-phase reforming of propanol-1, propane-1,2-diol and glycerol was performed at 498 K and 29.7 bar in a continuous reactor with platinum supported on a polymer-derived carbon, as a catalyst. The number of hydroxyl groups of the reactant influenced the product distribution. An unexpectedly long stabilization period − more than 150 h of time-on-stream − was found to be an important feature of the catalyst.

The presence of pharmaceutical compound residues in water bodies is becoming an increasingly serious problem. Various pharmaceuticals have been detected in raw municipal wastewaters, after wastewater treatment plant processes, and even in drinking water. Many common pharmaceuticals are bio-accumulating and they can have a harmful impact on aquatic and terrestrial organisms. In this work, pulsed corona discharge technology (PCD) is studied as a potential method for antibiotic compounds abatement. Two antibiotics, amoxicillin and doxycycline, were chosen as test pharmaceutical compounds. The aim of the study was to investigate the transformation kinetics of binary solutions (water – single antibiotic compound) and ternary solutions (water – two antibiotic compounds) of the compounds and to optimize operational parameters for improved oxidation performance. Ternary solutions were investigated to obtain data on transformation kinetics when two competing pharmaceutical molecules are present in the solution. The experiments showed that reactions of doxycycline oxidation are always first order reactions. Reaction of amoxicillin oxidation has second order in the case of experiments with binary solution in alkaline medium. In other cases, it has first order. The transformation products formed were identified and monitored based on liquid chromatography mass spectrometer analysis. OH-amoxicillin, amoxicillin pencilloic acid, OH-doxycycline and 2-OH-doxycycline had the largest peaks areas. All studied compounds and all transformation products can be easily oxidized by PCD. Approximately 1 kWh/m3 and 0.5 kWh/m3 delivered energy is enough for oxidation of great part of amoxicillin and doxycycline respectively. Low frequency, 50 pps, and high (pH = 12) are preferable for oxidation of both antibiotics from the energy consumption point of view.

The alkaline comet assay and a cell-free system were used to characterise DNA lesions induced by treatment with glycidamide (GA), a metabolite of the food contaminant acrylamide. DNA lesions induced by GA were sensitively detected when the formamidopyrimidine-DNA-glycosylase (Fpg) enzyme was included in the comet assay. We used LC-MS to characterise modified bases from GA-treated naked DNA with and without subsequent Fpg treatment. N7-GA-Guanine and N3-GA-Adenine aglycons were detected in the supernatant showing some depurination of adducted bases; treatment of naked DNA with Fpg revealed no further increase in the adduct yield nor occurrence of other adducted nucleobases. We treated human lymphocytes with GA and found large differences in DNA lesion levels detected with Fpg, depending on the duration and the pH of the lysis step. These lysis-dependent variations in GA-induced Fpg sensitive sites paralleled those observed after treatment of cells with methyl methane sulfonate (MMS). On the other hand, oxidative lesions (8-oxoGuanine) induced by a photoactive compound (Ro 12-9786) plus light, and also DNA strand breaks induced by X-rays, were detected largely independently of the lysis conditions. The results suggest that the GA-induced lesions are predominantly N7-GA-dG adducts slowly undergoing imidazole ring opening at pH 10 as in the standard lysis procedure; such structures are substrate for Fpg leading to strand breaks. The data suggest that the characteristic alkaline lysis dependence of some DNA lesions may be used to study specific types of DNA modifications. The comet assay is increasingly used in regulatory testing of chemicals; in this context, lysis-dependent variations represent a novel approach to obtain insight in the molecular nature of a genotoxic insult.

The presence of pharmaceuticals in surface water, drinking water, and wastewater has attracted significant concern because of the non-biodegradability, resistance, and toxicity of pharmaceutical compounds. The catalytic ozonation of an anti-inflammatory pharmaceutical, ibuprofen was investigated in this work. The reaction mixture was analyzed and measured by high-performance liquid chromatography (HPLC). Liquid chromatography-mass spectrometry (LC-MS) was used for the quantification of by-products during the catalytic ozonation process. Ibuprofen was degraded by ozonation under optimized conditions within 1 h. However, some intermediate oxidation products were detected during the ibuprofen ozonation process that were more resistant than the parent compound. To optimize the process, nine heterogeneous catalysts were synthesized using different preparation methods and used with ozone to degrade the ibuprofen dissolved in aqueous solution. The aim of using several catalysts was to reveal the effect of various catalyst preparation methods on the degradation of ibuprofen as well as the formation and elimination of by-products. Furthermore, the goal was to reveal the influence of various support structures and different metals such as Pd-, Fe-, Ni-, metal particle size, and metal dispersion in ozone degradation. Most of the catalysts improved the elimination kinetics of the by-products. Among these catalysts, Cu-H-Beta-150-DP synthesized by the deposition&ndash, precipitation process showed the highest decomposition rate. The regenerated Cu-H-Beta-150-DP catalyst preserved the catalytic activity to that of the fresh catalyst. The catalyst characterization methods applied in this work included nitrogen adsorption&ndash, desorption, scanning electron microscopy, transmission electron microscopy, and Fourier-transform infrared spectroscopy. The large pore volume and small metal particle size contributed to the improved catalytic activity.

Carbamazepine (CBZ), a widely used pharmaceutical compound, is one of the most detected drugs in surface waters. The purpose of this work was to identify an active and durable catalyst, which, in combination with an ozonation process, could be used to remove CBZ and its degradation products. It was found that the CBZ was completely transformed after ozonation within the first minutes of the treatment. However, the resulting degradation products, 1-(2-benzaldehyde)-4-hydro-(1H,3H)-quinazoline-2-one (BQM) and 1-(2-benzaldehyde)-(1H,3H)-quinazoline-2,4-dione (BQD), were more resistant during the ozonation process. The formation and degradation of these products were studied in more detail and a thorough catalytic screening was conducted to reveal the reaction kinetics of both the CBZ and its degradation products. The work was performed by non-catalytic ozonation and with six different heterogeneous catalysts (Pt-MCM-41-IS, Ru-MCM-41-IS, Pd-H-Y-12-EIM, Pt-H-Y-12-EIM, Pd-H-Beta-300-EIM and Cu-MCM-41-A-EIM) operating at two temperatures 20 &deg, C and 50 &deg, C. The influence of temperature on degradation kinetics of CBZ, BQM and BQD was studied. The results exhibited a notable difference in the catalytic behavior by varying temperature. The higher reactor temperature (50 &deg, C) showed a higher activity of the catalysts but a lower concentration of dissolved ozone. Most of the catalysts exhibited higher removal rate for BQM and BQD compared to non-catalytic experiments in both temperatures. The Pd-H-Y-12-EIM catalyst illustrated a higher degradation rate of by-products at 50 &deg, C compared to other catalysts.

In this work, ozone has been used to study the transformation of the antibiotic sulfadiazine (SDZ). SDZ and its transformation products was investigated using liquid chromatography coupled to mass spectrometry and using NMR. The results revealed that 6% of SDZ is transformed into 2-aminopyrimidine. A significant amount of SDZ undergoes a rearrangement reaction followed by ring-closing reactions. One of these products, SDZ-P15, is the main product after 240 min of ozonation. Almost 30% of SDZ transforms into SDZ-P15. SDZ was also transformed via the addition of one or more hydroxyl groups, via the oxidation of an amine group to a nitro group as well as via a bond cleavage reaction. Most of the intermediate products presented in this study have not previously been reported as SDZ transformation products formed using ozonation technology.

Printing technologies were recently introduced to the pharmaceutical field for manufacturing of drug delivery systems. Printing allows on demand manufacturing of flexible pharmaceutical doses in a personalized manner, which is critical for a successful and safe treatment of patient populations with specific needs, such as children and the elderly, and patients facing multimorbidity. Printing of pharmaceuticals as technique generates new demands on the quality control procedures. For example, rapid quality control is needed as the printing can be done on demand and at the point of care. This study evaluated the potential use of a handheld colorimetry device for quality control of printed doses of vitamin Bs on edible rice and sugar substrates. The structural features of the substrates with and without ink were also compared. A multicomponent ink formulation with vitamin B1, B2, B3, and B6 was developed. Doses (4 cm2) were prepared by applying 1–10 layers of yellow ink onto the white substrates using thermal inkjet technology. The colorimetric method was seen to be viable in detecting doses up to the 5th and 6th printed layers until color saturation of the yellow color parameter (b*) was observed on the substrates. Liquid chromatography mass spectrometry was used as a reference method for the colorimetry measurements plotted against the number of printed layers. It was concluded that colorimetry could be used as a quality control tool for detection of different doses. However, optimization of the color addition needs to be done to avoid color saturation within the planned dose interval.

The anti-epileptic drug carbamazepine (CBZ) receives growing attention due to slow biodegradation and inherent accumulation in the aquatic environment. The application of a gas-phase pulsed corona discharge (PCD) was investigated to remove CBZ from synthetic solutions and spiked wastewater effluent from a municipal wastewater treatment facility. The treated water was showered between high voltage (HV) wires and grounded plate electrodes, to which ultra-short HV pulses were applied. CBZ was readily oxidized and 1-(2-benzaldehyde)-4-hydroquinazoline-2-one (BQM) and 1-(2-benzaldehyde)-4-hydro-quinazoline-2,4-dione (BQD) were identified as the most abundant primary transformation products, which, contrary to CBZ ozonation data available in the literature, were further easily oxidized with PCD: BQM and BQD attributed to only a minor portion of the target compound oxidized. In concentrations commonly found in wastewater treatment plant effluents (around 5 µg L−1), up to 97% reduction in CBZ concentration was achieved at mere 0.3 kW h m−3 energy consumption, and over 99.9% was removed at 1 kW h m−3. The PCD application proved to be efficient in the removal of both the parent substance and its known transformation products, even with the competing reactions in the complex composition of wastewater.

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. Copyright © 2015 John Wiley & Sons, Ltd.

Structures of adducts formed in the reactions between a model oxoenal and the DNA bases were determined based on 2D NMR spectroscopy. Results obtained from quantum-mechanical studies indicated that two mechanisms can be involved in the generation of two pairs of stereomeric adducts of the oxoenal with 2′-deoxycytidine, and that the preference of one of the plausible routes depends on the structure of the forming product. Instability of one of these products leads to deamination of 2′-deoxycytidine. In the light of these results, stability of the structurally analogous 2′-deoxycytidine adducts of cis-2-butene-1,4-dial, the mutagenic metabolite of furan, was also studied, and it was demonstrated that these compounds undergo partial degradation resulting in the formation of 2′-deoxyuridine. This fact is of great importance with respect to biological consequences of the possible presence of such modifications in vivo. The data provide support to the hypothesis that in addition to 1,N6-etheno-2′-deoxyadenosine and 1,N2-etheno-2′-deoxyguanosine adducts of cis-2-butene-1,4-dial, also oxadiazabicyclooctaimine derivatives of 2′-deoxycytidine can significantly contribute to furan carcinogenic effects.

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.

The degradation of the pharmaceutical compound diclofenac in an aqueous solution was studied with an advanced oxidation method, catalytic ozonation. Diclofenac was destroyed in a few minutes by ozonation but several long-lasting degradation by-products were formed. For this reason, the combination of heterogeneous catalysts and ozonation was applied to eliminate them completely. The kinetics of the diclofenac degradation and the formation of by-products were thoroughly investigated. Loading of Pt on the catalysts resulted in an improvement of the activity. The Mesoporous Molecular Sieves (MCM) were one of the promising catalysts for the degradation of organic pollutants. In this study, six heterogeneous catalysts were screened, primarily MCM-22-100 catalysts with different Pt concentrations loaded via the evaporation-impregnation (EIM) method, and they were applied on the degradation of diclofenac. It was found that the presence of Pt improved the degradation of diclofenac and gave lower concentrations of by-products. The 2 wt % Pt-H-MCM-22-100-EIM demonstrated the highest degradation rate compared to the proton form, 1% or 5 wt % Pt concentration, i.e., an optimum was found in between. Pt-H-Y-12-IE and Pt-&gamma, Al2O3 (UOP)-IMP catalysts were applied and compared with the MCM-22 structure. Upon use of both of these catalysts, an improvement in the degradation of diclofenac and by-products was observed, and the 2 wt % Pt-H-MCM-22-100-EIM illustrated the maximum activity. All important characterization methods were applied to understand the behavior of the catalysts (X-ray powder diffraction, transmission electron microscopy, nitrogen physisorption, scanning electron microscopy, energy dispersive X-ray micro-analyses, pyridine adsorption-desorption with FTIR spectroscopy, X-ray photoelectron spectroscopy). Finally, leaching of Pt and Al were analyzed by inductively coupled optical emission spectrometry.

The biotransformation of the anti-inflammatory drug ibuprofen (IBF) was studied by exposing rainbow trout ( Oncorhynchus mykiss ) to IBF via intraperitoneal (i.p.) injection, and via water at four (0.17, 1.9, 13 and 145 μg L −1 ) exposure levels for 4 d. Following exposure, the bile was collected and analyzed by LC–MS/MS methods. The identification of the formed metabolites in i.p. injected fish bile was based on the exact mass determinations by a time-of-flight mass analyzer (Q–TOF–MS) and on the studies of fragments and fragmentation patterns of precursor ions by ion trap mass analyzer (IT-MS). In addition to unmetabolized IBF, several phase I and phase II metabolites were found in the bile. The main metabolites were acyl glucuronides and taurine conjugates of IBF and of hydroxylated IBFs. The bioconcentration factors (BCF bile ), defined as the ratio of the sum of IBF and its metabolites in fish bile to the concentration of IBF in water, was determined following enzymatic deconjugation and was found to range from 14 000 to 49 000. The highest BCF bile was found at the lowest exposure concentration (0.17 μg L −1 ). The results show that rainbow trout has a high capacity for biotransformation of IBF, and the exposure of fish to sub μg L −1 concentrations of IBF can be determined by the analyses of the biliary metabolites of the compound.

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

The dissemination of antibiotic resistance genes to the environment is an important factor causing increased prevalence of resistant pathogens. Manure is an important fertilizer, but it contains diverse resistance genes. Therefore, its application to fields may lead to increased abundance of resistance genes in the environment. Farming environments exposed to animal manure have not been studied extensively in countries with comparably low antibiotic use, such as Finland. The effects of manure storage and application to fields on the abundance of resistance genes were studied on two dairy cattle farms and two swine farms in southern Finland. Samples were taken from farms during the 2013 cropping season. Copy numbers of carbapenem (), sulfonamide (), and tetracycline () resistance genes were measured with quantitative polymerase chain reaction, and the data were analyzed using linear mixed models. The relative abundance of antibiotic resistance genes increased about fourfold in soil after manure application. Carbapenemase encoding was detected on all of the studied farms, which indicated that the gene is dispersed in the farm environment. The relative abundance of antibiotic resistance genes increased in stored manure compared with fresh manure roughly fivefold. This study shows that antibiotic resistance genes are disseminated on Finnish production animal farms. The spreading of resistance genes in farm-associated environments could possibly be limited by experimenting with new manure handling methods that could reduce the abundance of the genes in manure used for land application.

DNA–protein cross-links are formed upon exposure to a variety of physical and exogenous, as well as endogenous chemical agents. This type of damage poses a threat to genomic integrity. Among the agents capable of inducing DNA–protein cross-links bifunctional electrophiles arising from cellular processes deserve particular attention. Representatives of such electrophiles include glyoxal, methylglyoxal and malonaldehyde. Herein, we report that glyoxal and methylglyoxal adducts of 2′-deoxyadenosine formed in the presence of malonaldehyde {M1Gx-dA [8-(diformylmethyl)-3-(2′-deoxy-β-D-ribofuranosyl)imidazo[2,1-i]purine], and M1MGx-dA [8-(diformylmethyl)-7-methyl-3-(2′-deoxy-β-D-ribofuranosyl)imidazo[2,1-i]purine], respectively}, display high reactivity towards lysine derivatives. In reactions with Nα-acetyllysine M1Gx-dA was found to form three adducts whereas M1MGx-dA reacted with the lysine congener to form two stable products. All compounds were isolated and their structures determined on the basis of 2D NMR spectroscopy. Formation of the analogous products was shown in the individual reactions of M1Gx-dA and M1MGx-dA with Nϵ-acetyllysine. Mechanisms proposed for formation of all characterised compounds are also discussed. This study reports identification of structures for a potentially new class of DNA–protein cross-links.

Pharmaceuticals are ubiquitous in surface waters as a consequence of discharges from municipal wastewater treatment plants. However, few studies have assessed the bioavailability of pharmaceuticals to fish in natural waters. In the present study, passive samplers and rainbow trout were experimentally deployed next to three municipal wastewater treatment plants in Finland to evaluate the degree of animal exposure. Pharmaceuticals from several therapeutic classes (in total 15) were analyzed by liquid chromatography-tandem mass spectrometry in extracts of passive samplers and in bile and blood plasma of rainbow trout held at polluted sites for 10 d. Each approach indicated the highest exposure near wastewater treatment plant A and the lowest near that of plant C. Diclofenac, naproxen, and ibuprofen were found in rainbow trout, and their concentrations in bile were 10 to 400 times higher than in plasma. The phase I metabolite hydroxydiclofenac was also detected in bile. Hence, bile proved to be an excellent sample matrix for the exposure assessment of fish. Most of the monitored pharmaceuticals were found in passive samplers, implying that they may overestimate the actual exposure of fish in receiving waters. Two biomarkers, hepatic vitellogenin and cytochrome P4501A, did not reveal clear effects on fish, although a small induction of vitellogenin mRNA was observed in trout caged near wastewater treatment plants B and C.

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. Environ. Toxicol. Chem. 2012; 31: 1781–1787. © 2012 SETAC

Wastewater treatment plants (WWTPs) are commonly considered as the main source of pharmaceuticals in surface waters. Here, however, we show that an open-air festival, attracting approximately 10,000 visitors per year at the shores of River Fyris upstream of Uppsala WWTP, can temporarily result in a higher pharmaceutical input into the river water than the WWTP. Studying the influence of Uppsala Reggae festival on the occurrence of ten commonly used acidic and basic pharmaceuticals upstream, in the effluent, and downstream of the Uppsala WWTP, we found that occasional heavy rainfalls during the festival in 2008 severely increased the mass flows of all pharmaceuticals at the WWTP upstream site. Also, strong increases in ammonium (210-fold), nitrate (21-fold), and total nitrogen (21-fold) mass flows were observed. The pharmaceutical mass flows at the upstream site were up to 3.4 times higher than those observed in the WWTP effluent. In contrast, in 2009, the festival was not accompanied with rainfalls and no major additional input of pharmaceuticals and nitrogen was observed. The findings of this study give new insights into risk assessments and are relevant for monitoring programmes.

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. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:3386–3395, 2011

Using the freshwater annelid Lumbriculus variegatus (Oligochaeta), the presence of cytochrome P450 (CYP) isozymes was investigated by analyzing metabolites of the polycyclic aromatic hydrocarbon (PAH) pyrene in treatments with and without the CYP inhibitor piperonyl butoxide (PBO). The results show a low biotransformation capability of L. variegatus (7% of total pyrene body burden as metabolites at 168 h). Addition of PBO resulted in a significant reduction of metabolites, suggesting the presence of a CYP in L. variegatus. Besides 1-hydroxypyrene, three peaks representing unknown metabolites were detected in LC-FLD (liquid chromatography with fluorescence detection) chromatograms of L. variegatus. Deconjugations showed that sulfonation and glucosidation are involved in the formation of these unknowns. Further studies with the time of flight mass analyzer provided the identification of the glucose-sulfate conjugate of 1-hydroxypyrene. The same metabolites were detected in the solvent-nonextractable fraction by incubation of the tissue residues with proteinase K, suggesting that part of these metabolites are bound to proteins. Overall, the slow biotransformation of pyrene by L. variegatus (involving CYP) supports the use of this species in standard bioaccumulation tests; however, the tissue-bound metabolite fraction described in the current study deserves further investigation for its toxicity and availability to upper trophic levels through diet.

The anti-inflammatory drug naproxen (NPX) has been found as a micropollutant in river water downstream the discharge points of wastewater treatment plants (WWTP). In this study, rainbow trout (Oncorhynchus mykiss) was exposed to NXP and the uptake and metabolism of the drug was studied.Following exposure through intraperitoneal injection (i.p., 0.5 mg NPX/100 g fish biomass) and through water (1.6 μg L(-1)), the bile was collected and analyzed with various LC-MS/MS methods. The identification of the formed metabolites in i.p. injected fish was based on the exact mass determinations by a time-of-flight mass analyzer (Q-TOF-MS) and on the studies of fragments and fragmentation patterns of precursor ions by an ion trap mass analyzer (IT-MS).No matter the exposure route, the main metabolites were found to be acyl glucuronides of NPX and of 6-O-desmethylnaproxen. Also, unmetabolized NPX was detected in the bile. The total bioconcentration factors (BCF(total-bile)) of NPX and the metabolites in the bile of fish exposed through water ranged from 500 to 2,300.The findings suggest that fish living downstream WWTPs may take up NPX and metabolize the compound. Consequently, NPX and its metabolites in bile can be used to monitor the exposure of fish to NPX.

Acrylamide (AA) is produced in many types of food products cooked or processed at high temperature. AA is metabolized to the epoxide glycidamide (GA), which can bind to deoxyguanosine and deoxyaden ...

An analytical method for the quantification of thyroid hormones (3,5,3',5'-tetraiodo-L-thyronine, 3,3',5-triiodo-L-thyronine, 3,3',5'-triiodothyronine, 3,5-diiodothyronine, 3,3'-diiodothyronine) in different water matrices has been developed. The method, consisting of solid phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), was validated for tap and surface water as well as raw and treated waste water. The limits of quantifications (LOQs) were lowest in tap water, where they ranged from 1.1 to 13.3 ng L(-1), and highest in raw wastewater (10.5-84.9 ng L(-1)). Of the target analytes 3,5,3',5'-tetraiodo-L-thyronine (T(4)) could be quantified in the influent and effluent of a waste water treatment plant (WWTP) in Finland. The study showed that despite a relatively high removal rate during treatment (66%), part of the incoming T(4) will reach the aquatic environment and, due to the high endocrine activity of this compound, further studies are needed in order to assess its environmental fate and impact on natural ecosystems.

The seasonal variations in the occurrence of carbamazepine, atenolol, metoprolol, sotalol, and acebutolol were studied at seven sites along River Fyris from December 2007 to December 2008. Samples were collected from the effluent of a waste water treatment plant (WWTP), at one upstream site, and five downstream sites of the WWTP. During one occasion in May 2008, water samples were collected at different locations and depths in the recipient lake. All analytes except of acebutolol were present in both the river and the lake at quantifiable amounts at all sampling occasions. Carbamazepine was found in similar concentrations (about 90 ng L(-1)) at all sampling sites and all studied depths (0.5-40 m) in the lake, indicating high environmental persistence of this compound. A clear seasonal pattern was observed for the natural attenuation of the beta-blockers in the river, with the highest attenuation occurring in summer and the lowest in winter. The loss of beta-blockers on a distance of 1320 m reached up to 75% during summer time but was insignificant during winter. The seasonal variations in the loss followed the seasonal variations in water temperature and chlorophyll a mass flow suggesting that biotransformation and adsorption are the main processes responsible for the loss of the studied pharmaceuticals in River Fyris downstream the WWTP.

In this study, seasonal variations in the concentration profile of four analgesics and one lipid regulator were monitored on their way from a wastewater treatment plant (WWTP) effluent, along a river, and into a lake.From December 2007 to December 2008, water samples were collected monthly (n=12) from an upstream point, the effluent, four downstream points of the WWTP, and at the point where the river merges with the lake, and the concentrations of ibuprofen, naproxen, bezafibrate, diclofenac, and ketoprofen were determined. The analytical methodology involved solid-phase extraction of the target compounds from water samples followed by liquid chromatography coupled with tandem mass spectrometry for compound separation and detection.The studied pharmaceuticals were found in the effluent at concentrations ranging from 31 to 1,852 ng l(-1) depending on the season. In the river and lake, the concentrations were much lower (6-400 ng l(-1)) mainly due to dilution but also to a season-dependent contribution from natural transformation processes. The mean mass flow of all analgesics was highest during winter while the highest mean mass flow of the lipid regulator bezafibrate was observed in spring.The WWTP is the main source of the target compounds in the aquatic environment. The observed winter accumulation signifies the importance of natural transformation processes, which can only be estimated based on mass flow data, on the fate of pharmaceuticals in the environment.

The formation of stable and potentially hazardous compounds as a result of photochemical transformation of pharmaceutical substances in the aquatic environment implies a demand for standard compounds within environmental analysis. The major phototransformation products of diclofenac are comprised of substituted diphenylamines and carbazoles. Substituted diphenylamines were synthesized by Ullmann condensation reactions between anilines and halobenzenes. Monochlorocarbazoles were obtained from palladium-catalyzed intramolecular coupling reactions of monochlorinated diphenylamines, photocyclization of dichlorinated diphenylamines or by direct chlorination of carbazole. The availability of synthetic photoproducts of diclofenac is of critical importance for further studies on the environmental fate as well as the ecotoxicological effects of the drug in the environment.

Each year, large quantities of pharmaceuticals are consumed worldwide for the treatment and prevention of human and animal diseases. Although the drugs and the metabolites observed in the wastewaters and in the environment are present at concentrations several orders of magnitude lower than the concentrations required to exert their effects in humans or animals, their long-term impact on the environment is commonly not known. In this study, the occurrence of six antihistamines, which are used for the relief of allergic reactions such as hay fever, was determined in sewage treatment plants wastewaters and in recipient river waters. The occurrence of the antihistamines cetirizine, acrivastine, fexofenadine, loratadine, desloratadine and ebastine in sewage treatment plants wastewaters and in recipient river waters was studied. The analytical procedure consisted of solid-phase extraction of the water samples followed by liquid chromatography separation and detection by a triple-quadrupole mass spectrometer in the multiple reaction mode. Cetirizine, acrivastine and fexofenadine were detected in both influent and effluent wastewater samples at concentration levels ranging from about 80 to 220 ng/L, while loratadine, desloratadine and ebastine could not be detected in any samples. During sewage treatment, the concentration of the antihistamines dropped by an average of 16–36%. Furthermore, elevated concentrations of antihistamines were observed in samples collected during the season of most intensive plant pollen production, i.e. in May. In the river water samples, the relative pattern of occurrence of cetirizine, acrivastine and fexofenadine was similar to that in the wastewater samples; although the concentration of the compounds was substantially lower (4–11 ng/L). The highest concentrations of the studied drugs were observed near the discharging point of the sewage treatment plant. The highest concentrations of antihistamines in STP wastewaters correlate with the outbreak of allergic reaction caused by high amounts of plant pollens in the air. The analysis results of the river water samples show that the antihistamines are carried far away from the effluent discharge points. They may account for a part of the mix of pharmaceuticals and of pharmaceutical metabolites that occur downstream of STPs. Antihistamines are poorly degraded/eliminated under the biological treatment processes applied in the wastewater treatment plants and, consequently, they are continuously being discharged along with other drugs to the aquatic environment. As a huge quantity and variety of drugs and their metabolites are continuously discharged to rivers and the sea, the compounds should be considered as contaminants that may possess risks to the aquatic ecosystem. Further studies are urgently needed on the environmental fate of the antihistamines and other pharmaceuticals in the aquatic environment. These studies should be concerned with the stability of the compounds, their transformation reactions and the identity of the transformation products, the distribution of drugs and their uptake and effects in organisms. On the basis of these studies, the possible environmental hazards of pharmaceuticals may be assessed.

The adduct 3-beta-D-ribofuranosyl-3,7,8,9-tetrahydropyrimido[1,2-i]purin-8-ol (2), obtained from adenosine and epichlorohydrin, underwent ring fission at basic conditions. The initial ring-opening took place at C2 of the pyrimidine unit resulting in 2-(5-amino-1-beta-D-ribofuranosyl-imidazol-4-yl)-1,4,5,6-tetrahydropyrimidin-5-ol (3). Also the tetrahydropyrimidine ring of 3 could be opened resulting in 5-amino-1-(beta-D-ribofuranosyl)-imidazole-4-(N-3-amino-2-hydroxyl-propyl)-carboxamide (4). In hot acid conditions, 2 was both deglycosylated and ring-opened yielding 2-(5-amino-imidazol-4-yl)-1,4,5,6-tetrahydropyrimidin-5-ol (7) as the final product. When reacting 3 with CS(2) or HNO(2) ring-closure took place and 3-beta-D-ribofuranosyl-3,4,7,8,9-pentahydropyrimido[1,2-i]purin-8-ol-5-thione (5), and 3-beta-D-ribofuranosyl-imidazo[4,5-e]-3,7,8,9-tetrahydropyrimido[1,2-c][1,2,3]triazine-8-ol (6), respectively, were obtained. Also, the pyrimidine ring of the epichlorohydrin adduct with adenine, 10-imino-5,6-dihydro-4H,10H-pyrimido[1,2,3-cd]purin-5-ol (10), underwent ring fission and the product was identified as 3-hydroxy-1,2,3,4-tetrahydroimidazo[1,5-a]pyrimidine-8-carboximidamide (11).

Environmental estrogens are substances that imitate the effects of endogenous estrogens. Effluents from municipal wastewater treatment plants are known to contain substances with estrogenic activity including steroidal estrogens and xenoestrogens. In the current study, a combination of biological and chemical analysis was applied to determine the estrogenic activity in municipal wastewater effluents in Finland. The male three-spined stickleback (Gasterosteus aculeatus) hepatocyte assay with vitellogenin induction as an endpoint was used for the detection of estrogenic activity in solid phase extracts of wastewater effluents, and 17beta-estradiol (E2) as a positive control. The wastewater extracts and E2 were found to induce vitellogenin production. The extracts were also subjected to chromatographic fractionation and the collected fractions were assayed. The only active fraction was the one in which E2, estrone and ethynylestradiol were eluted. Its activity corresponded to the activity of the original wastewater extract. The LC-MS/MS analyses of the wastewater extracts showed that the concentration of estrone was about 65 ng L(-1), the concentration of E2 was less than 1 ng L(-1), while estriol and 17alpha-ethynylestradiol could not be detected. These findings showed that the activity of the wastewater extracts and the chromatographic fraction was much higher than the activity which could have been expected on the base of the chemical analysis. This strongly indicates that other compounds, possibly acting by additivity or synergism, are playing a major role in the induced vitellogenin production by the hepatocytes.

Acrolein, an important industrial chemical and environmental contaminant, has been shown to interact with nucleic acids in vitro and in vivo. In this study, we examined the reactivity of acrolein towards thymidine and calf-thymus double- and single-stranded DNA in aqueous buffered solutions. LC-MS Analyses of the reaction mixture of acrolein with thymidine showed the formation of five structurally different adducts. The structures of the products were determined on the basis of mass spectrometry, UV absorbance, and (1)H- and (13)C-NMR spectroscopy. The adducts were identified as 3-(3-oxopropyl)thymidine (dT1), 3-[(tetrahydro-2,4-dihydroxypyran-3-yl)methyl]thymidine (dT2), 2-(hydroxymethyl)-5-(thymidin-3-yl)pent-2-enal (dT3), 3-hydroxy-2-methylidene-5-(thymidin-3-yl)pentanal (dT4), and 2-[(thymidin-3-yl)methyl]penta-2,4-dienal (dT5). The adducts dT2-dT5 were formed in reaction of dT1 with acrolein. In the reaction of acrolein with calf-thymus DNA, dT1 was the only adduct detected in the DNA hydrolysate.

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.

Four emerging micropollutants ibuprofen, diclofenac, estrone (E1) and 17α-ethinylestradiol (EE2) were studied in large laboratory-scale wastewater treatment plants (WWTPs) with high nitrifying activity. Activated sludge (AS) with sludge retention times (SRTs) of 12days and 14days in sequencing batch reactors (SBRs) and 30days, 60days and 90days in membrane bioreactors (MBRs) were examined at 8°C and 12°C. Concentrations of pharmaceuticals and their main metabolites were analysed in liquid phase and solid phase of AS by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A remarkable amount of contaminants were detected in solids of AS, meaning the accumulation of micropollutants in bacterial cells. The biodegradation rate constants (Kbiol) were affected by SRT and temperature. MBR with a 90-day SRT showed the best results of removal. Conventional SBR process was inefficient at 8°C showing Kbiol values lower than 0.5lgSS(-1)d(-1) for studied micropollutants.

Our previous work has shown that treatment of nucleosides with malonaldehyde simultaneously with acetaldehyde affords stable conjugate adducts. In the present study we demonstrate that conjugate adducts are also formed in calf thymus DNA when incubated with the aldehydes. The adducts were identified in the DNA hydrolysates by their positive ion electrospray MS/MS spectra, by coelution with the 2'-deoxynucleoside standards, and, in the case of adducts exhibiting fluorescent properties, also by LC using a fluorescence detector. In the hydrolysates of double-stranded DNA (ds DNA), two deoxyguanosine and two deoxyadenosine conjugate adducts were detected and in single-stranded DNA (ss DNA) also, the deoxycytidine conjugate adduct was observed. The guanine base was the major target for the malonaldehyde-acetaldehyde conjugates and 2'-deoxyguanosine adducts were produced in ds DNA at levels of 100-500 adducts/10(5) nucleotides (0.7-3 nmol/mg DNA).

The fragmentation pattern of 30 compounds belonging to different classes of the lignan family was studied by liquid chromatography-electrospray ionization ion-trap mass spectrometry. On the basis of the observed fragmentation patterns, identification of different types of lignans was achieved. For example, dibenzylbutyrolactone lignans showed a characteristic fragmentation pathway by the loss of 44 Da (CO(2)) from the lactone moiety, whereas dibenzylbutanediols showed a loss of 48 Da by a combined loss of formaldehyde and water from the 1,4-butanediol moiety. Lignan glycosides readily lost the sugar residue to give the parent lignan as their primary product ion. In addition, several compound-specific fragmentations were observed and used for identification of individual compounds.A versatile method for analyses of lignans was developed using LC separation on a C8 column followed by fragmentation and detection of ions produced in the ion trap.

The occurrence of four beta blockers, one antiepileptic drug, one lipid regulator, four anti-inflammatories, and three fluoroquinolones was studied in a river receiving sewage effluents. All compounds but two of the fluoroquinolones were observed in the water above their limit of quantification concentrations. The highest concentrations (up to 107 ng L(-1)) of the compounds were measured during the winter months. The river water was passed to a pilot-scale drinking water treatment plant, and the elimination of the pharmaceuticals was followed during the treatment. The processes applied by the plant consisted of ferric salt coagulation, rapid sand filtration, ozonation, two-stage granular activated carbon filtration (GAC), and UV disinfection. Following the coagulation, sedimentation, and rapid sand filtration, the studied pharmaceuticals were found to be eliminated only by an average of 13%. An efficient elimination was found to take place during ozonation at an ozone dose of about 1 mg L(-1) (i.e., 0.2-0.4 mg of O3/ mg of TOC). Following this treatment, the concentrations of the pharmaceuticals dropped to below the quantification limits with the exception of ciprofloxacin. Atenolol, sotalol, and ciprofloxacin, the most hydrophilic of the studied pharmaceuticals, were not fully eliminated during the GAC filtrations. All in all, the treatment train was found to very effectively eliminate the pharmaceuticals from the rawwater. The only compound that was found to pass almost unaffected through all the treatment steps was ciprofloxacin.

The occurrence of eight pharmaceuticals (beta-blockers: acebutolol, atenolol, metoprolol and sotalol; antiepileptic: carbamazepine; fluoroquinolone antibiotics: ciprofloxacin, norfloxacin, ofloxacin) were assessed in the raw and treated sewage of 12 sewage treatment plants (STPs) in Finland. The average concentrations in the raw and treated sewage ranged from 100 to 1060 ng L(-1) and from24 to 755 ng L(-1), respectively. The average daily loads ranged from 36 to 405 mg/1000 inh and from 2 to 302 mg/1000 inh, respectively. In the treatment plants, fluoroquinolones were eliminated by80%. Carbamazepine was not eliminated during the treatment and in fact even higher concentrations were frequently found in the treated than in the raw sewages. The increase in concentration was shown to be most likely due to enzymatic cleavage of the glucuronic conjugate of carbamazepine and release of the parent compound in the treatment plant. The beta-blockers were eliminated in average by less than 65% and the elimination varied greatly between the treatment plants. Especially the dilution of raw sewage by rainwater and a consequent decrease in the hydraulic retention time of a treatment plant was found to deteriorate the elimination of the beta-blockers. The work shows that especially carbamazepine and the beta-blockers may reach the recipient waters and there is a need to enhance their elimination in the sewage treatment plants. In this attempt, a denitrifying biofilter as a tertiary treatment could be of minor importance since in this study it did not result in further elimination of the target compounds.

LC-MS analysis of the reaction mixture of 2′-deoxycytidine and acrolein in phosphate buffer under physiological conditions showed the formation of three major product peaks. The products were characterized as cyclic adducts comprised of one or two units derived from acrolein. The first (8) and third (9) eluting peaks were each found to be a pair of diastereomers of a two-ring-fused adduct, 6,9-dihydroxy-2-(2′-deoxy-β-D-erythro-pentofuranosyl)-2,5,6,7,8,9-hexahydro-4H-2,3a,6a-triazaphenalen-3-one, whilst the second eluting peak (7) was identified as a one-ring-fused adduct, 2-hydroxy-7-(2′-deoxy-β-D-erythro-pentofuranosyl)-2,3,4,7-tetrahydropyrimido[1,6-a]pyrimidin-6-one. The reaction of 1-methylcytosine with acrolein was also examined resulting in the formation of an additional regioisomeric two-ring-fused adduct, 2-hydroxy-7-methyl-3,4,7,9,10,10a-hexahydro-2H-1-oxa-4a,7,8a-triazaphenanthren-8-one, not observed in the corresponding reaction with 2′-deoxycytidine. The structures, stereochemistry and conformational analysis of the adducts and their decomposition products were resolved by spectrometric and spectroscopic studies. From the incubation of acrolein with double- and single-stranded DNA and subsequent LC-MS/MS analysis (in multiple reaction monitoring mode) of the hydrolysate, compounds were detected corresponding (i.e. identical Rt and MS) to the peaks that represented the pair of diastereomers 7 and 9.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

International audience; Six products containing either fluorosurfactants or fluorinated polymers have been evaluated for hydrophobization of marble stones by a total immersion method. Successful hydrophobization was verified by water contact angle and capillary absorption measurements before and after intentional UV degradation of the outmost modified layer. Optimization of treatment time and solution concentration concluded that for the best performing product, Capstone FS-63, a 24h immersion in a 10 vol% aqueous solution was required to obtain marble stones fully protected toward water absorption. The presented surface modifications could significantly increase the product lifespan of a variety of marble products.

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.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.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.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.

Analytical method was developed which allowed for the detection of four beta blockers (acebutolol, atenolol, metoprolol and sotalol), an antiepileptic drug (carbamazepine) and three fluoroquinolone antibiotics (ciprofloxacin, ofloxacin and norfloxacin) with a single pre-treatment and chromatographic method. The method included an isolation and concentration procedure using solid phase extraction, a separation step using high performance liquid chromatography and a detection procedure applying triple quadrupole mass spectrometry, which was working in the multiple reaction monitoring mode. The method was validated for ground, surface and sewage influent and effluent waters. Due to ion suppression in the electrospray source, the signals monitored for the analytes were less intense in sewage waters compared to ground and surface waters. The limits of quantification were as low as 1 ng L(-1) in ground water and 3.5 ng L(-1) in sewage influent. The method was successfully applied to the determination of the target compounds in raw and treated sewages of three treatment plants in Finland and in their recipient rivers. The results showed that many of the studied compounds pose a moderate to high persistency in sewage treatment as well as in the recipient rivers. The analytical protocol presented may be used for more in-depth studies on the occurrence and fate of these commonly used pharmaceuticals in the sewage treatment plants and in the aquatic environment.

Epichlorohydrin (a probable human carcinogen) was allowed to react with adenosine and the adducts were characterized by NMR and UV spectroscopy, and mass spectrometry. The adduct initially formed was 1-(3-chloro-2-hydroxypropyl)-adenosine, which subsequently ring closures to 1,N6-(2-hydroxypropyl)-adenosine at neutral and basic conditions. At acid conditions, the N-1 adduct undergoes a slow deamination to yield 1-(3-chloro-2-hydroxypropyl)-inosine. Minor adducts identified were 7-(3-chloro-2-hydroxypropyl)-adenosine and 3-(3-chloro-2-hydroxypropyl)-adenosine which are easily deglycosylated, and an adduct where the epichlorohydrin residue was attached to the sugar moiety of adenosine. A diadduct, 1,N6-(2-hydroxypropyl)-N6-(3-chloro-2-hydroxypropyl)-adenosine was also identified. The reaction of epichlorohydrin with calf thymus DNA gave 1,N6-(2-hydroxypropyl)-deoxyadenosine and 3-(3-chloro-2-hydroxypropyl)-adenine (major adduct).

A poly(N-methylaniline) (PNMA) film was obtained by chronoamperometry on tin oxide (TO) in dimethylformamide DMF containing 0.5 M sulphuric acid. The PNMA film formation was monitored by in situ UV–vis spectroscopy. A detailed electropolymerization mechanism and reaction pathway of N-methylaniline (NMA) is proposed based on mass spectroscopy (MS) and NMR analysis. The NMA repeating units (both in the film and in the soluble part) were found to be partially dealkylated during electropolymerization. NMA was also electropolymerized in different solvents such as propylene carbonate (PC) and acetonitrile (ACN). Our results show that protonation is not a necessary condition to initiate the electropolymerization of NMA, but it may play a key role for the propagation of longer conjugated chains. The influence of solvents on the film formation and the function of protons are discussed in this paper.

The removal of selected pharmaceuticals (diclofenac, ibuprofen, bezafibrate, carbamazepine and sulfamethoxazole) by chemical coagulation was studied. Jar test experiments were done in MilliQ water, in lake water and in commercial humic acid solutions using aluminium (pH 6) and ferric sulphate (pH 4.5). The concentrations of the pharmaceuticals in the studied water samples were determined by HPLC analysis and UV detection. In MilliQ water coagulation, the pharmaceuticals were poorly removed (10%) with the exception of diclofenac, which was removed up to 66% with ferric sulphate. This compound was also the only pharmaceutical removed (30%) during the lake water coagulation with ferric sulphate. In the presence of dissolved humic matter, diclofenac as well as ibuprofen and bezafibrate could be removed by ferric sulphate coagulation. The removal of diclofenac reached a maximum of 77%, while 50% of ibuprofen and 36% of bezafibrate were removed. Hence, a high amount of high-molecular-weight dissolved organic matter enhanced the removal of ionisable pharmaceuticals. The non-ionisable compounds, carbamazepine and sulfamethoxazole, were not affected by the coagulation processes studied. Although conditions such as high humic material content, low coagulation pH and ferric coagulant increase the removal of certain ionic pharmaceuticals, it can be concluded that by coagulation it is not possible to entirely remove pharmaceuticals from water.

The occurrence of five acidic pharmaceuticals, ibuprofen, naproxen, ketoprofen, diclofenac and bezafibrate, in seven different sewage treatment plants (STP) and three receiving waters were determined. The analytical procedure included solid phase extraction, liquid chromatographic separation and detection by a triple-quadrupole mass spectrometer. The studied pharmaceuticals were found in all the STPs. The pattern of the occurrence of individual compounds was the same in every STP and matched the consumption figures reported in the literature. Ibuprofen is the most used pharmaceutical in Finland and was accordingly found to be the most abundant compound in the raw sewage. In the treatment processes, the highest removal rate was observed for ibuprofen and the lowest for diclofenac, 92%±8% and 26%±17%, respectively. Due to the incomplete removal in the STPs, the pharmaceuticals were found in rivers at the discharge points of the STP effluents. Downstream from the discharge points, the concentrations decreased significantly mainly due to dilution in the river water. The risk to the aquatic environment was estimated by a ratio of measured environmental concentration (MEC) and predicted no-effect concentration (PNEC). At the concentrations the compounds were found in the surface waters, they should not pose risk for the aquatic environment. However, at dry seasons and/or during malfunctions of STPs, ibuprofen could be associated with a risk in small river systems.

The restricted rotation about the conjoining bond in a series of 4″-substituted bi-imidazole nucleosides {5-amino-4-[4″-R-imidazol-2″-yl]-1-(β-d-ribofuranosyl)-1H-imidazole; where R=H, methyl, hydroxymethyl, oxalo, formyl} due to intramolecular hydrogen bonding between N-3″ and the N-6 protons concomitant with prototropic tautomerism has been examined using multinuclear (1H, 13C and 15N) experimental NMR. Substitution at the 4″ position causes the interconversion, whilst still an intramolecular process, to yield complex spectra as the dynamic process consists of a two-site exchange between non-degenerate tautomeric forms (asymmetric sites). The preferred tautomers were identified experimentally in each case and compared with theoretically determined structures geometry optimized using density functional theory (DFT) at the B3LYP/6–31G(d,p) level of theory on which gauge-independent atomic orbital-DFT (GIAO-DFT) computations at the B3LYP/cc-pVTZ level of theory were applied to calculate the chemical shifts of the 1H, 13C and 15N nuclei. Both the site and the extent of protonation of the bi-imidazole nucleosides were also similarly ascertained using the same methodology. Protonation at the pyridine-type nitrogen (N-3″) of the outer imidazole ring, the principle site of protonation, effectively eliminated the barrier to rotation about the conjoining bond yielding time-averaged spectra experimentally. Copyright © 2004 John Wiley & Sons, Ltd.