Pharmaceuticals and iodinated contrast media in a hospital wastewater: A case study to analyse their presence and characterise their environmental risk and hazard.

This work analyses the presence of twenty-five pharmaceutical compounds belonging to seven different therapeutic groups and one iodinated contrast media (ICM) in a Spanish medium-size hospital located in the Valencia Region. Analysis of the target compounds in the hospital wastewater was performed by means of solid phase extraction (SPE) followed by liquid chromatography-tandem mass spectrometry analysis (HPLC-MS/MS). A screening level risk assessment combining the measured environmental concentrations (MECs) with dose-response data based on Predicted No Effect Concentration (PNEC) was also applied to estimate Hazard Quotients (HQs) for the compounds investigated. Additionally, the environmental hazard associated to the various compounds measured was assessed through the calculation of the Persistence, Bioaccumulation and Toxicity (PBT) Index, which categorizes compounds according to their environmentally damaging characteristics. The results of the study showed the presence of twenty-four out of the twenty-six compounds analysed at individual concentrations ranging from 5 ng L(-1) to 2 mg L(-1). The highest concentrations corresponded to the ICM iomeprol, found at levels between 424 and 2093 µg L(-1), the analgesic acetaminophen (15-44 µg L(-1)), the diuretic (DIU) furosemide (6-15 µg L(-1)), and the antibiotics (ABIs) ofloxacin and trimethoprim (2-5 µg L(-1)). The lowest levels corresponded to the anti-inflammatory propyphenazone, found at concentrations between 5 and 44 ng L(-1). Differences in terms of concentrations of the analysed compounds have been observed in all the therapeutic groups when comparing the results obtained in this and other recent studies carried out in hospitals with different characteristics from different geographical areas and in different seasons. The screening level risk assessment performed in raw water from the hospital effluent showed that the analgesics and anti-inflammatories (AAFs) acetaminophen, diclofenac, ibuprofen and naproxen, the antibiotics (ABIs) clarithromycin, ofloxacin and trimethoprim, and the ß-blocker (BBL) propranolol were present at concentrations leading to HQ values higher than 10, thus indicating high risk. When applying a factor to take into account potential dilution and degradation processes, only the compound ibuprofen showed a HQ higher than 1. Likewise, the cumulative HQ or Toxic Units (TUs) calculated in the raw water for each of the therapeutic groups studied showed that these three classes of drugs were at concentrations high enough to potentially generate high risk to aquatic organisms while taking into account possible dilution and degradation processes only one of them, the AAFs can be considered to represent high risk. Finally, the environmental hazard assessment performed showed that the AAFs diclofenac and ibuprofen and the ABI clarithromycin have the highest, maximum value of 9 of PBT Index due to their inherent environmentally damaging characteristics of persistence, bioaccumulation and toxicity. The methodology followed in the present case study can be taken as a novel approach to classify and categorize pharmaceuticals on the basis of their occurrence in hospital effluents, their derived environmental risks, and their associated environmental hazard. This classification becomes important because it can be used as a model or orientation for hospitals in the process of developing environmentally sustainable policies and as an argument to justify the adoption of advanced, specific treatments for hospital effluents before being discharged into the public sewage system.

Ibuprofen exposure in Lemna gibba L.: Evaluation of growth and phytotoxic indicators, detection of ibuprofen and identification of its metabolites in plant and in the medium.

Ibuprofen (IBU) is detected worldwide in water bodies due to the incomplete removal by wastewater treatments. Contrasting results have been reported on the toxicity of IBU on aquatic biomonitor plants such as duckweed, and no data about IBU detection and metabolism in plants has been reported. In this work, the effects of 1 mg L(-1) IBU on Lemna gibba L. were monitored in an 8-day laboratory test. In particular, an increase in frond number (+12%) and multiplication rate (+10%) while no variations in photosynthetic pigment content were observed. Moreover, UPLC-HRMS analysis of the presence of IBU and its metabolites in plants and in the growth medium was performed. The results showed that, besides IBU, 11 IBU metabolites were detected in plants. Among the IBU metabolites, hydroxyl- and dihydroxyl-IBU were found, whereas carboxyl-IBU was undetectable. Interestingly, some IBU metabolites were detected in the plant growth solution at the end of the IBU treatment, while no IBU products were found in the IBU solution without plants, suggesting a role for L. gibba in IBU metabolism. The findings of this work represent an important step for a better evaluation of the effects of IBU and its metabolites in duckweed, with notable implications for the eco-toxicological assessment of IBU in the aquatic ecosystem.

FM19G11 reverses endothelial dysfunction in rat and human arteries through stimulation of the PI3K/Akt/eNOS pathway, independently of mTOR/HIF-1α activation.

BACKGROUND AND PURPOSE: FM19G11 up-regulates mammalian target of rapamycin (mTOR)/hypoxia inducible factor-1α (HIF-1α) and PI3K/Akt pathways, which are involved in endothelial function. We evaluated the effects of FM19G11 on defective endothelial vasodilatation in arteries from rats and humans and investigated the mechanisms involved. EXPERIMENTAL APPROACH: Effects of chronic in vivo administration of FM19G11 on aortic endothelial vasodilatation were evaluated together with ex vivo treatment in aortic and mesenteric arteries from control and insulin-resistant rats (IRR). Its effects on vasodilator responses of penile arteries (HPRAs) and corpus cavernosum (HCC) from men with vasculogenic erectile dysfunction (ED) (model of human endothelial dysfunction) were also evaluated. Vascular expression of phosphorylated-endothelial NOS (p-eNOS), phosphorylated-Akt (p-Akt) and HIF-1α was determined by immunodetection and cGMP by elisa. KEY RESULTS: Chronic administration of FM19G11 reversed the impaired endothelial vasodilatation in IRR. Ex vivo treatment with FM19G11 also significantly improved endothelium-dependent vasodilatation in aorta and mesenteric arteries from IRR. These effects were accompanied by the restoration of p-eNOS and cGMP levels in IRR aorta and were prevented by either NOS or PI3K inhibition. p-Akt and p-eNOS contents were increased by FM19G11 in aortic endothelium of IRR. FM19G11-induced restoration of endothelial vasodilatation was unaffected by mTOR/HIF-1α inhibitors. FM19G11 also restored endothelial vasodilatation in HPRA and HCC from ED patients. CONCLUSIONS AND IMPLICATIONS: Stimulation of the PI3K/Akt/eNOS pathway by FM19G11 alleviates impaired NO-mediated endothelial vasodilatation in rat and human arteries independently of mTOR/HIF-1α activation. This pharmacological strategy could be beneficial for managing pathological conditions associated with endothelial dysfunction, such as ED.

Total synthesis of (+)-7-deoxypancratistatin from furan.

A new total synthesis of (+)-7-deoxypancratistatin 1 has been accomplished in 19 steps (8% overall yield) from two readly available compounds, furan and trans-1,2-bis(phenylsulfonyl)ethylene.

Studies in marine polypropionate synthesis: total synthesis of (-)-baconipyrone C.

[reaction--see text] An asymmetric total synthesis of the unusual siphonariid metabolite, (-)-baconipyrone C (3), is described. Key steps included a tin(II)-mediated aldol coupling for the preparation of the carboxylic acid 17 and two different boron-mediated aldol additions leading to alcohol 8. Ester formation using modified Yamaguchi conditions gave 24, leading on PMB deprotection to (-)-baconipyrone C.

Quantitative analysis of ES-285, an investigational marine anticancer drug, in human, mouse, rat, and dog plasma using coupled liquid chromatography and tandem mass spectrometry.

A method was developed for the quantitative analysis of the novel anticancer agent ES-285 (spisulosine; free base) in human, mouse, rat, and dog plasma using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry in order to support pre-clinical and clinical studies with the drug. Sample preparation was carried out by protein precipitation with acetonitrile, containing isotopically labeled (d(3)) ES-285 as internal standard. Aliquots of 10 micro l of the supernatant were injected directly on to an Inertsil ODS-3 column (50 x 2.0 mm i.d., 5 micro m). Elution was carried out using methanol-10 mM ammonium formate (pH 4) in water (80 : 20, v/v) pumped at a flow-rate of 0.2 ml min(-1) with a run time of 8 min. Multiple reaction monitoring chromatograms obtained on an API365 triple-quadrupole mass spectrometer were used for quantification. The lower limit of quantitation (LLOQ) was 10 ng ml(-1) in human, mouse, rat, and dog plasma and the linear dynamic range extended to 500 ng ml(-1). A full validation of the method was performed in human plasma, and partial validations were performed in mouse, rat and dog plasma. Accuracies and precisions were <20% at the LLOQ concentration and <15% for all other concentrations in all matrices. ES-285 was stable during all steps of the assay. Thus far this method has been used successfully to analyze over 500 samples in pre-clinical trials, and will be implemented in the planned clinical phase I studies.

Pharmaceuticals and organic pollution mitigation in reclamation osmosis brines by UV/H2O2 and ozone.

One significant disadvantage of using reverse osmosis (RO) for reclamation purposes is the need to dispose of the RO retentates. These retentates contain a high concentration of micropollutants, effluent organic matter (EfOM) and other inorganic constituents, which are recalcitrant to biological treatment and may impact the environment. The occurrence of 11 pharmaceuticals (concentrations ranging from 0.2 to 1.6 µg L(-1)) and their mitigation in RO retentates by a UV/H2O2 process and ozonation was studied using a wide range of oxidant dosages. Eleven pharmaceuticals were identified at. Initial observed kinetic constants (kobs) were calculated for the different pharmaceuticals. Other typical wastewater parameters were also monitored during the UV/H2O2 and ozonation reactions. The range for kobs was found to be 0.8-12.8L mmol O3(-1) and 9.7-29.9 L mmol H2O2(-1) for the ozonation and UV/H2O2 process, respectively. For ozonation, Atenolol, Carbamazepine, Codeine, Trimethoprim and Diclofenac showed the lowest initial kobs (in the order mentioned). Atenolol and Carbamazepine appeared as the most ozone resistant pharmaceuticals, exhibiting the lowest percentage of elimination at low ozone doses. On the other hand, despite the non-selectivity of HO, differences in the initial kobs were also observed during the UV/H2O2 process. Trimethoprim, Paroxetine and Sulfamethoxazole exhibited the lowest initial kobs values (in the order mentioned). Trimethoprim and Paroxetine also exhibited the lowest percentage removal when low H2O2 doses were assayed. The compounds that were identified as problematic during ozonation were more efficiently removed by the UV/H2O2 process. UV/H2O2 generally appeared to be a more efficient technology for removing pharmaceuticals from RO brines compared to ozonation.

Light-induced catalytic transformation of ofloxacin by solar Fenton in various water matrices at a pilot plant: mineralization and characterization of major intermediate products.

This work investigated the application of a solar driven advanced oxidation process (solar Fenton), for the degradation of the antibiotic ofloxacin (OFX) in various environmental matrices at a pilot-scale. All experiments were carried out in a compound parabolic collector pilot plant in the presence of doses of H2O2 (2.5 mg L(-1)) and at an initial Fe(2+) concentration of 2 mg L(-1). The water matrices used for the solar Fenton experiments were: demineralized water (DW), simulated natural freshwater (SW), simulated effluent from municipal wastewater treatment plant (SWW) and pre-treated real effluent from municipal wastewater treatment plant (RE) to which OFX had been spiked at 10 mg L(-1). Dissolved organic carbon removal was found to be dependent on the chemical composition of the water matrix. OFX mineralization was higher in DW (78.1%) than in SW (58.3%) at 12 mg L(-1) of H2O2 consumption, implying the complexation of iron or the scavenging of hydroxyl radicals by the inorganic ions present in SW. On the other hand, the presence of dissolved organic matter (DOM) in SWW and RE, led to lower mineralization per dose of H2O2 compared to DW and SW. The major transformation products (TPs) formed during the solar Fenton treatment of OFX, were elucidated using liquid chromatography-time of flight-mass spectrometry (LC-ToF-MS). The transformation of OFX proceeded through a defluorination reaction, accompanied by some degree of piperazine and quinolone substituent transformation while a hydroxylation mechanism occurred by attack of the hydroxyl radicals generated during the process leading to the formation of TPs in all the water matrices, seven of which were tentatively identified. The results obtained from the toxicity bioassays indicated that the toxicity originates from the DOM present in RE and its oxidation products formed during the photocatalytic treatment and not from the TPs resulted from the oxidation of OFX.