Biological and photochemical degradation of cytostatic drugs under laboratory conditions.

Cytostatic drugs, used in chemotherapy, have emerged as new environmental contaminants due to their recurrent presence in surface waters and genotoxic effects. Yet, their degradability and environmental fate is largely unknown. The aim of this study was to determine the degradation kinetics of 16 cytostatic drugs, prioritized according to their usage and occurrence in hospital and wastewater treatment plants (WWTP) effluents, through the following laboratory scale processes: hydrolysis, aerobic biodegradation, UV-C photolysis, UV-C/H2O2 and simulated solar radiation. Some drugs were unstable in milli-Q water (vincristine, vinblastine, daunorubicin, doxorubicin and irinotecan); others were photodegraded under UV-C light (melphalan and etoposide) but some others were found to be recalcitrant to biodegradation and/or UV-C, making necessary the use of advanced oxidation processes (AOPs) such as UV-C/H2O2 for complete elimination (cytarabine, ifosfamide and cyclophosphamide). Finally, radiation in a solar box was used to simulate the fate of cytostatic drugs in surface waters under natural radiation and complete removal was not observed for any drug. The degradation process was monitored using liquid chromatography coupled to high resolution mass spectrometry and pseudo-first order kinetic degradation constants were calculated. This study provides new data on the degradability of cytostatic compounds in water, thus contributing to the existing knowledge on their fate and risk in the environment.

Decomposition of Iodinated Pharmaceuticals by UV-254 nm-assisted Advanced Oxidation Processes.

Iodinated pharmaceuticals, thyroxine (a thyroid hormone) and diatrizoate (an iodinated X-ray contrast medium), are among the most prescribed active pharmaceutical ingredients. Both of them have been reported to potentially disrupt thyroid homeostasis even at very low concentrations. In this study, UV-254 nm-based photolysis and photochemical processes, i.e., UV only, UV/H2O2, and UV/S2O82-, were evaluated for the destruction of these two pharmaceuticals. Approximately 40% of 0.5µM thyroxine or diatrizoate was degraded through direct photolysis at UV fluence of 160mJcm-2, probably resulting from the photosensitive cleavage of C-I bonds. While the addition of H2O2 only accelerated the degradation efficiency to a low degree, the destruction rates of both chemicals were significantly enhanced in the UV/S2O82- system, suggesting the potential vulnerability of the iodinated chemicals toward UV/S2O82- treatment. Such efficient destruction also occurred in the presence of radical scavengers when biologically treated wastewater samples were used as reaction matrices. The effects of initial oxidant concentrations, solution pH, as well as the presence of natural organic matter (humic acid or fulvic acid) and alkalinity were also investigated in this study. These results provide insights for the removal of iodinated pharmaceuticals in water and/or wastewater using UV-based photochemical processes.

Photo-Fenton treatment of valproate under UVC, UVA and simulated solar radiation.

The abatement of valproic acid sodium salt (VA) via photo-Fenton process was investigated to evaluate the effect of irradiation type. Three different light sources have been used: UVA (black light blue lamps, BLB reactor), UVC (UVC reactor) and simulated sunlight in a Solarbox (SB). Using the highest concentrations of Fe2+ (10mgL-1) and H2O2 (150mgL-1), 100% of VA degradation was observed in BLB and UVC devices, and 89.7% in Solarbox. Regarding mineralization, 67.4% and 76.4% of TOC conversion were achieved in BLB and UVC, respectively. In Solarbox, mineralization was negligible. Treated solutions under UVA or UVC radiation became biodegradable (BOD5/COD≥0.25), which was not observed in Solarbox where BOD5/COD achieved was only 0.20. Regarding to toxicity (Vibrio Fischeri method), all processes have promoted the overall toxicity reduction of VA solution. Transformation products were identified by a LC-ESI-TOF mass spectrometer, and degradation pathways were proposed. Operating costs and the energy needed by mg of VA removed were estimated and compared, for the different installations, showing that UVA can remove around 3 times more VA than SB and 2 times more VA than UVC, under the same conditions.

Identification and characterization of photodegradation products of metoprolol in the presence of natural fulvic acid by HPLC-UV-MSn.

Metoprolol is a ß-blocker highly prescribed for the treatment of heart diseases. It is not efficiently removed in wastewater treatment plants and it has been detected not only in the treated effluents, but also in natural waters. Thus, the knowledge of its fate in the environment is an important issue, and photodegradation is an important degradation pathway. While direct photodegradation of metoprolol by solar light is not relevant, there is evidence in the literature that it suffers indirect photodegradation and a few studies have been published showing the important role of dissolved humic matter as photo-sensitizer. However, the identification of the photoproducts formed in the presence of humic matter is very poor, since only 2 photoproducts had been identified. This study investigated the degradation of metoprolol under simulated solar radiation and in the presence of fulvic acids (FA) extracted from a river. During the photodegradation experiments we observed the formation of new compounds which were separated and tentatively identified by HPLC-UV-ESI-MSn. At least 16 compounds were tentatively identified, including the 2 compounds previously identified in the literature and 4 new compounds which had not been detected by other authors as degradation products of metoprolol, even when submitted to artificial degradation processes.

Chromatography and high-resolution mass spectrometry for the characterization of the degradation products of the photodegradation of amidosulfuron: an analytical approach.

Simulated sunlight irradiation causing degradation of amidosulfuron, a pyrimidinylsulfonylurea herbicide, has been investigated in aqueous solution. The main degradation products were followed up by ultrahigh-pressure liquid chromatography with a UV detector (UHPLC-UV) and identified by combining ultrahigh-pressure liquid chromatography-mass spectrometry (UHPLC-MS) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). On the basis of the retrosynthetic analysis, the most identified degradation products were mainly due to the losses of methylsulfamic acid (CH5NO3S), sulfocarbamic acid (CH3NO5S), carbamic acid (CH3NO2), methyl(methylsulfonyl)sulfamic acid (C2H7NO5S2), N-methylmethanesulfonamide (C2H7NO2S), and sulfonic acid (H2SO4) molecules. Accordingly, O and S-demethylation as well as hydroxylation processes were also observed. Sum formulas of the main degradation products were assigned, and a mechanical pathway is proposed.

Effect of 50 Hz sinusoidal electromagnetic field on the kinetics of 14CO2 exhalation after [14C]-N-nitrosodiethylamine administration in mice.

N-Nitrosodiethylamine (NDEA) has been identified as a typical environmental carcinogen. Its metabolism was studied in mice under the influence of an electromagnetic field (EMF). After intraperitoneal administration of [14C]-NDEA, 0.2 microCi/100 g body weight resulted in 22.8% of the total radioactivity exhaled as 14CO2 within 1 h. Mice were exposed to a 50 Hz, 2 mT (rms) electromagnetic field, 8 h/day for 8 weeks. There was a significant increase in the metabolic turnover of [14C]-NDEA into 14CO2 at the end of both 6 and 8 weeks of field exposure, i.e., 26.9% and 37.4% respectively. The enhanced capacity of mice to metabolize NDEA after the exposure to EMF may result in animals with a smaller amount of the bioactive carcinogen burden, thereby indicating a protective role of 2 mT EMF in a whole animal study.

Investigation of the stability of medicinal additives in animal feedingstuffs to prepare reference feeds.

The stability of several medicinal additives in cattle, pig and poultry feeds has been monitored. The feeds were stored at various temperatures under different conditions; processes such as freeze-drying, gamma-irradiation and pelletization were also applied. The medicinal additives appeared to be more stable in the feeds stored at reduced temperatures and under conditions that totally exclude light. Processing of feeds and storage at elevated temperature appeared to reduce the content of the medicinal additives examined.