Ultraviolet photolysis of four typical cardiovascular drugs: mechanisms, influencing factors, degradation pathways, and toxicity trends.

The cardiovascular drugs (CDDs), such as metoprolol (MET), atenolol (ATE), bezafibrate (BZB), and atorvastatin (ATO), have been frequently detected in the water environment. They can cause potential threats to the ecological environment and human health due to their "pseudo-persistence" effect. In this study, the photolysis kinetics, degradation mechanisms, by-products, influencing factors, and acute toxicity of these four typical CDDs under polychromatic ultraviolet irradiation (200-400 nm) were investigated. The results showed that the photolysis of ATE, BZB, MET, and ATO all followed pseudo-first-order kinetics, and their average photon quantum yields of the wavelength studied were 0.14×10-2, 0.33×10-3, 0.78×10-4, and 0.24×10-4 mol einstein-1, respectively. Singlet oxygen (1O2), hydroxyl radical (·OH), and the triplet-excited state of the cardiovascular drug (3CDD*) were all involved in the photolysis while 1O2 was the dominator. The effects of NO3-, Cl-, HCO3-, and humic acid (HA) on the photolysis were the combination of light-shielding, quenching, and excitation of reactive species. Seven, four, four, and nine photolysis products of ATO, BZB, ATE, and MET were identified, respectively, and their possible degradation pathways were proposed. The acute toxicity of ATE was basically unchanged during photolysis; however, ATO, BZB, and MET toxicity all increased due to the generation of ketonization and hydroxylation products.

BiOCl facilitated photocatalytic degradation of atenolol from water: Reaction kinetics, pathways and products.

Atenolol (ATL), a kind of largely used beta-blockers, has been widely detected in the aquatic environment, which could cause adverse impact on human beings. In this study, bismuth oxychloride (BiOCl) photocatalyst was synthesized and applied to remove ATL in the aqueous system under simulated natural light. Emphasis was laid on the reaction kinetics and the impact of natural organic matter (NOM) (0-20 mg/L). Possible transformation pathways were systematically investigated based on identification of reaction products via liquid chromatography-mass spectrometry (LC-MS). As a consequence, BiOCl presents highly photocatalytic efficiency yielding up to nearly 100% ATL conversion after 60 min of interaction, together with fairly high photostability evidenced by considerably efficient removal of ATL after 10 catalytic cycles. Four kinds of possible products are detected using LC-MS in the process of reaction, indicating possible transformation ways of ATL photocatalysis. NOM has an inhibiting impact on the removal of ATL and influences the products distribution. This study provides an emerging nanocatalyst for ATL photodegradation and could eventually lead to development of novel methods to control pharmaceutical contamination in water.

Degradation of atenolol via heterogeneous activation of persulfate by using BiOCl@Fe3O4 catalyst under simulated solar light irradiation.

Efficient oxidative degradation of pharmaceutical pollutants in aquatic environments is of great importance. This study used magnetic BiOCl@Fe3O4 catalyst to activate persulfate (PS) under simulated solar light irradiation. This degradation system was evaluated using atenolol (ATL) as target pollutant. Four reactive species were identified in the sunlight/BiOCl@Fe3O4/PS system. The decreasing order of the contribution of each reactive species on ATL degradation was as follows: h+ ≈ HO· > O2·- > SO4·-. pH significantly influenced ATL degradation, and an acidic condition favored the reaction. High degradation efficiencies were obtained at pH 2.3-5.5. ATL degradation rate increased with increased catalyst and PS contents. Moreover, ATL mineralization was higher in the sunlight/BiOCl@Fe3O4/PS system than in the sunlight/BiOCl@Fe3O4 or sunlight/PS system. Nine possible intermediate products were identified through LC-MS analysis, and a degradation pathway for ATL was proposed. The BiOCl@Fe3O4 nanomagnetic composite catalyst was synthesized in this work. This catalyst was easily separated and recovered from a treated solution by using a magnet, and it demonstrated a high catalytic activity. Increased amount of the BiOCl@Fe3O4 catalyst obviously accelerated the efficiency of ATL degradation, and the reusability of the catalyst allowed the addition of a large dosage of BiOCl@Fe3O4 to improve the degradation efficiency.

Phototransformation of wastewater-derived trace organic contaminants in open-water unit process treatment wetlands.

Open-water cells in unit process treatment wetlands can be used to exploit sunlight photolysis to remove trace organic contaminants from municipal wastewater effluent. To assess the performance of these novel systems, a photochemical model was calibrated using measured photolysis rates for atenolol, carbamazepine, propranolol, and sulfamethoxazole in wetland water under representative conditions. Contaminant transformation by hydroxyl radical ((•)OH) and carbonate radical ((•)CO3(-)) were predicted from steady-state radical concentrations measured at pH values between 8 and 10. Direct photolysis rates and the effects of light screening by dissolved organic matter on photolysis rates were estimated using solar irradiance data, contaminant quantum yields, and light screening factors. The model was applied to predict the land area required for 90% removal of a suite of wastewater-derived organic contaminants by sunlight-induced reactions under a variety of conditions. Results suggest that during summer, open-water cells that receive a million gallons of water per day (i.e., about 4.4 × 10(-2) m(3) s(-1)) of nitrified wastewater effluent can achieve 90% removal of most compounds in an area of about 15 ha. Transformation rates were strongly affected by pH, with some compounds exhibiting faster transformation rates under the high pH conditions associated with photosynthetic algae at the sediment-water interface and other contaminants exhibiting faster transformation rates at the circumneutral pH values characteristic of algae-free cells. Lower dissolved organic carbon concentrations typically resulted in increased transformation rates.

Photodegradation kinetics and transformation products of ketoprofen, diclofenac and atenolol in pure water and treated wastewater.

Pharmaceutical compounds such as ketoprofen, diclofenac and atenolol are frequently detected at relatively high concentrations in secondary effluents from wastewater treatment plants. Therefore, it is important to assess their transformation kinetics and intermediates in subsequent disinfection processes, such as direct ultraviolet (UV) irradiation. The photodegradation kinetics of these compounds using a medium pressure (MP) lamp was assessed in pure water, as well as in filtered and unfiltered treated wastewater. Ketoprofen had the highest time- and fluence-based rate constants in all experiments, whereas atenolol had the lowest values, which is consistent with the corresponding decadic molar absorption coefficient and quantum yield. The fluence-based rate constants of all compounds were evaluated in filtered and unfiltered wastewater matrices as well as in pure water. Furthermore, transformation products of ketoprofen, diclofenac and atenolol were identified and monitored throughout the irradiation experiments, and photodegradation pathways were proposed for each compound. This enabled the identification of persistent transformation products, which are potentially discharged from WWTP disinfection works employing UV photolysis.

The role of dissolved organic matters in the aquatic photodegradation of atenolol.

Atenolol (ATL) is a photostable and hydrolysis resistant beta-blocker and has been frequently detected in natural water. In this study, mechanism on aquatic photodegradation of ATL was investigated with an emphasis on the role of dissolved organic matters (DOMs) as well as other natural water compositions (nitrate, bicarbonate and ferric ions). Significant acceleration of photodegradtion of ATL was observed in the presence of each DOMs added, namely Suwannee River Fulvic Acid (SRFA), Suwannee River Humic Acid (SRHA), Nordic Lake Fulvic Acid (NOFA) and Nordic Lake Humic Acid (NOHA). Hydroxyl radical (•OH) was determined as the main reactive species in this process, instead of singlet oxygen or excited triplet of DOM. Addition of these four DOMs all inhibited photodegradation of ATL in nitrate solutions through reducing nitrated-derived •OH and screening photons absorbed by nitrate. No loss of ATL was detected in bicarbonate solution with or without DOMs. Bicarbonate exhibited a scavenger of •OH derived from DOMs. However, in the presence of iron species, photodegradation of ATL was significantly enhanced by the addition of each DOM, due to the high yield of •OH in the photoprocess of Fe(III)-DOM complex. The photoproducts distribution of ATL demonstrated that SRFA promote the hydroxylation on aromatic ring in the presence of nitrate and reduce the ketone moiety to alcohol in the system of ferric ions. Our findings indicate that DOMs should be considered in aquatic photoprocesses of organic pollutants induced by themselves as well as other coexisting photoactive water compositions.

Drugs degrading photocatalytically: Kinetics and mechanisms of ofloxacin and atenolol removal on titania suspensions.

The conversion of the antibiotic ofloxacin and the beta-blocker atenolol by means of TiO(2) photocatalysis was investigated. Irradiation was provided by a UVA lamp at 3.37x10(-6)einstein/s photon flux, while emphasis was given on the effect of catalyst type and loading (50-1500mg/L), initial substrate concentration (5-20mg/L), initial pH (3-10) and the effect of H(2)O(2) (0.07-1.4mM) as an additional oxidant on substrate conversion and mineralization in various matrices (i.e. pure water, groundwater and treated municipal effluent). Conversion was assessed measuring sample absorbance at 288 and 224nm for ofloxacin and atenolol, respectively, while mineralization measuring the dissolved organic carbon. Degussa P25 TiO(2) was found to be more active than other TiO(2) samples for either substrate degradation, with ofloxacin being more reactive than atenolol. Conversion generally increased with increasing catalyst loading, decreasing initial substrate concentration and adding H(2)O(2), while the effect of solution pH was substrate-specific. Reaction rates, following a Langmuir-Hinshelwood kinetic expression, were maximized at a catalyst to substrate concentration ratio (w/w) of 50 and 15 for ofloxacin and atenolol, respectively, while higher ratios led to reduced efficiency. Likewise, high concentrations of H(2)O(2) had an adverse effect on reaction, presumably due to excessive oxidant scavenging radicals and other reactive species. The ecotoxicity of ofloxacin and atenolol to freshwater species Daphnia magna was found to increase with increasing substrate concentration (1-10mg/L) and exposure time (24-48h), with atenolol being more toxic than ofloxacin. Photocatalytic treatment eliminated nearly completely toxicity and this was more pronounced for atenolol.

Characterization of atenolol transformation products on light-activated TiO2 surface by high-performance liquid chromatography/high-resolution mass spectrometry.

We have studied the photocatalytic transformation of atenolol, 4-[2-hydroxy-3-[(1-methyl)amino]propoxyl]benzeneacetamide, a cardioselective beta-blocking agent used to treat cardiac arrhythmias and hypertension, under simulated solar irradiation using titanium dioxide as photocatalyst. The investigation involved monitoring drug decomposition, identifying intermediate compounds, assessing mineralization, and evaluating toxicity. High-performance liquid chromatography (HPLC) coupled to high-resolution mass spectrometry (HRMS) via an electrospray ionization (ESI) interface was a powerful tool for the identification and measurement of the degradation products; 23 main species were identified. Intermediates were characterized through their chromatographic behavior and evolution kinetics, coupled with accurate mass information. Through the full analysis of MS and MS(n) spectra and a comparison with parent drug fragmentation pathways, the diverse isomers were characterized. Neither atenolol nor the intermediates formed exhibit acute toxicity. All intermediates are easily degraded and no compound identified could withstand 2 h irradiation. Photomineralization of the substrate in terms of carbon mineralization and nitrogen release was rapid and, within 4 h of irradiation, organic nitrogen and carbon were completely mineralized.

The use of multi-frequency EPR techniques to identify the radicals produced in irradiated beta-blockers.

The identification of radicals trapped in irradiated drugs can be very intricate. A multi-frequency electron paramagnetic resonance (EPR) study is proposed to resolve this problem. The Q-band (ca. 34 GHz) comparison with X-band (ca. 9 GHz) did not show significant differences for the four beta-blockers studied (atenolol, esmolol, nadolol and propranolol). The use of a higher frequency (285 GHz) was required. It enabled us to determine the g-tensor values of the radicals present in atenolol and esmolol, respectively, g1 = 2.0086, g2 = 2.0059 and g3 = 2.0021 and g1 = 2.0066, g2 = 2.0044 and g3 = 2.0021. The latter was assigned as a phenoxyl radical, which can not be the case for the former. Therefore, radicals produced in esmolol may result from a more complex mechanism than the abstraction followed by the diffusion of an H atom inside the solid. In addition, two molecules as similar as atenolol and esmolol hydrochloride do not contain the same radicals after irradiation. These two conclusions drawn from the EPR results on beta-blockers show clearly the importance of continuing the investigations on radiolytic mechanisms in solid-state drugs.

Photodegradation studies on Atenolol by liquid chromatography.

The photostability of the beta-blocker drug Atenolol was evaluated at pH 9, 7.4 and 4.0. The drug was exposed to UVA-UVB radiations and the photoproducts were detected by reversed phase LC methods. The photodegradation was found to increase with the pH value decreasing. The major photodegradation product at pH 7.4 was identified as 2-(4-hydroxyphenyl)acetamide. The LC method developed for routine analyses (column: C-18 Alltima; mobile phase: TEA acetate (pH 4; 0.01 M)-acetonitrile 96:4) was found to be suitable for the stability indicating determination of Atenolol in pharmaceutical dosage forms.