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.

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.

Enhancement of Fenton and photo-Fenton processes at initial circumneutral pH for the degradation of the ß-blocker metoprolol.

The need for acidification in the Fenton and photo-Fenton process is often outlined as one of its major drawbacks, thus in this work the acidification of the Metoprolol (MET) is avoided by the addition of resorcinol (RES), which is used to simulate model organic matter. The experiments were carried out at natural pH (6.2) with different Fe(2+) (1, 2.5, 5, and 10 mg/L) and H2O2 (25, 50, 125 and 150 mg/L) concentrations. The performance of MET and RES degradation was assessed along the reaction time. Working with the highest concentrations (5 and 10 mg/L of ferrous iron and 125 and 150 mg/L of H2O2) more than 90% of MET and RES removals were reached within 50 and 20 min of treatment, respectively, by Fenton process. However a low mineralization was achieved in both cases, likely, due to by-products accumulation. Regarding to photo-Fenton process, within 3 min with the highest iron and hydrogen peroxide concentrations, a complete MET degradation was obtained and 95% of RES conversion was achieved. Parameters such Total Organic Carbon, Chemical Oxygen Demand, and AOS were measured. Intermediates were identified and MET degradation path was proposed in the presence of resorcinol. Finally, a comparison between Fenton and photo-Fenton processes at acid pH and at initial circumneutral pH was discussed. The positive effect of RES on Fenton and photo-Fenton systems has been confirmed, allowing the work at circumneutral pH.

Degradation characteristics of metoprolol during UV/chlorination reaction and a factorial design optimization.

Metoprolol (MTP), a hypertension depressor, has been increasingly detected even after conventional water treatment processes. In this study, the removal of MTP was compared using chlorination (Cl2), UV-C photolysis, and UV/chlorination (Cl2/UV) reactions. The results showed that the UV/chlorination reaction was most effective for MTP removal. MTP removal during UV/chlorination reaction was optimized under various conditions of UV intensity (1.1-4.4 mW/cm(2)), chlorine dose (1-5 mg/L as Cl2), pH (2-9), and dissolved organic matter (DOM, 1-4 mgC/L) using a two-level factorial design with 16 experimental combinations of the four factors. Among the factors examined, DOM scavenging by OH radicals was the most dominant in terms of MTP removal during UV/chlorination reaction. The established model fit well with the experimental results using to various water samples including surface waters, filtered and tap water samples. The optimized conditions (UV intensity=4.4 mW/cm(2), [Cl2]=5 mg/L, pH 7, and [DOM]=0.8-1.1 mgC/L) of the model removed more than 78.9% of MTP for filtered water samples during UV/chlorination reaction. Using LC-MS/MS, five byproducts of MTP (molecular weight: 171, 211, 309, 313, and 341, respectively) were identified during UV/chlorination reaction. Based on this information, the MTP transformation mechanism during UV/chlorination was suggested. Our results imply that applying UV/chlorination process after filtration stage in the water treatment plant (WTP) would be the most appropriate for effective removal of MTP.

The effect of ionizing radiation on metoprolol.

The influence of ionising radiation on physico-chemical properties of metoprolol tartrate (MT) in solid phase was studied. The compound was irradiated by radiation produced by a beam of high-energy electrons in an accelerator, in doses from 25 to 400 kGy, and the possible changes in the samples were detected by organoleptic analysis (colour, forms, clarity), chromatographic and spectrometric methods. Already at the standard sterilisation dose of 25 kGy, the presence of free radicals (0.3764 × 10(16) spin/g) and a decrease in the melting point by 1°C were noted. At higher doses of irradiation products of radiolysis appeared (100 kGy) and the colour was changed from white to pale cream (200 kGy). Our observation was that with increasing mass loss of MT after irradiation with 100, 200 and 400 kGy, the concentration of free radicals increased from 1.0330 to 1.6869 × 10(16) spin/g. The radiolytic yield of total radiolysis was 4.54 × 10(7) mol/J for 100 kGy, 7.42 × 10(7) mol/J for 200 kGy and 4.74 × 10(7) mol/J for 400 kGy. No significant changes were observed in the character of FT-IR spectra, but in UV an increase in intensity of the band at the analytical wavelength was noted. As follows from the results MT shows high radiochemical stability for the typical sterilisation doses 25-50 kGy, and will probably be able to be sterilised by radiation in the dose of 25 kGy.

UV-C radiation based methods for aqueous metoprolol elimination.

The endocrine disruptor metoprolol has been oxidised in aqueous solution by means of the systems UV-C, UV-C/H(2)O(2), UV-C/percarbonate, UV-C/monopersulfate, UV-C/TiO(2), UV-C/H(2)O(2)/TiO(2) and photo-Fenton. From simple photolysis experiments the quantum yield of metoprolol has been calculated (roughly 5x10(-3) mol Einstein(-1) at circumneutral pH). Addition of free radicals promoters significantly enhanced the metoprolol depletion rate. Mineralization degree was negligible when no promoter was added, while low values were achieved in the presence of either inorganic peroxides or titanium dioxide. The combination of radiation, hydrogen peroxide and TiO(2) increased the mineralization level up to values in the proximity of 45-50% under the best conditions investigated. The photo-Fenton process was the best system in terms of total oxidation (mineralization degree 70%) when optimum conditions were applied.

Radical mechanisms in the radiosterilization of metoprolol tartrate solutions.

PURPOSE: Study of the radical mechanisms in the radiosterilization of metoprolol tartrate aqueous solutions in order to determine the parameters governing its radiostability. METHODS: Pulse radiolysis with pseudo-first-order kinetics to measure Ihe reaction rate constants of hydrated electrons and hydroxyl radicals with metoprolol tartrate. Chemsimul was used to solve the decay kinetics of transients and to simulate the radiolysis of metoprolol tartrate solutions. RESULTS: Hydrated electrons react with metoprolol and the tartrate ion with rate constants of 6.8 x 10(7) M(-1) s(-1) and 1.7 x 10(7) M(-1) s(-1), respectively. Hydroxyl radicals react with metoprolol and the tartrate ion with rate constants of 5.2 x 10(9) M(-1) s(-1) and 5.5 x 10(8) M(-1) s(-1), respectively. The hydroxyl-metoprolol transients are found to scavenge the superoxide anion (5.5 x 10(10) M(-1) s(-1)), react with oxygen (1.0 x 10(8) M(-1) s(-1)), and follow a biradical decay (2.0 x 10(8) M(-1) s(-1). A simplified radical mechanism is used to simulate the loss of potency of metoprolol tartrate aqueous solutions during radiosterilization. CONCLUSIONS: To decrease the loss of potency of metoprolol tartrate. the sterilization dose must be lowered and very high dose rates used.