Related to improving persistence assessment of active pharmaceutical ingredients (APIs), direct aqueous photolysis of beta-blockers: propranolol (hydrochloride salt), atenolol, and metoprolol (succinate salt) were investigated by exposing the samples (0.0003-10 mg L(-1)) to a solar irradiator (filtered xenon lamp: 290-800 nm) at 20-26 degrees C. Results suggested that direct photolysis in optically dilute solutions followed pseudo first-order kinetics. The measured half-lives of propranolol, atenolol, and metoprolol were approximately 16, 350, and 630 h, respectively. These were 3-5 orders of magnitude slower than the estimated minimum half-lives. The measured half-lives were related to day light surface conditions by comparing the light intensity of the lamp and the sun at different latitudes and seasons. Major direct photolysis products were identified from propranolol that led to a proposed reaction pathway, involving ring oxidation, rearrangement, and deoxygenation. Electron paramagnetic resonance (EPR) spectroscopy results confirmed that at least one carbon-based radical intermediate was formed during the direct photolysis of propranolol in aqueous solutions. The overall results demonstrated that with fast direct photolysis half-lives, propranolol is unlikely to be persistent in natural waters. Further work is needed to investigate indirect photolysis of atenolol and metoprolol in surface waters in order to understand the overall persistence of these APIs in the environment.

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In order to improve the understanding of the fate and behaviour of pharmaceuticals in the environment there is a need to investigate in-stream depletion mechanisms, e.g. phototransformation of active pharmaceutical ingredients (APIs) in natural surface waters. In this study, abiotic and biotic degradation of selected beta-blockers was measured simultaneously in non-sterilised and sterilised river waters and deionised water (DIW) under simulated sunlight (lambda: 295-800 nm) and dark conditions, and at environmentally relevant concentrations, i.e.

Transformation products of pharmaceuticals formed by human metabolism within sewage treatment plant or receiving waters are predicted, in most cases, to be less toxic than the parent compound to common aquatic species. However, there is little available data to demonstrate whether this is generally the case. In the present study, a framework was developed to guide testing of transformation products using phototransformation of the beta-blocker propranolol to test the hypothesis for this particular transformation route. Phototransformation is an important depletion mechanism of some pharmaceuticals in surface waters with fast reaction rate constants at environmentally relevant conditions. Samples of propranolol in deionized water (DIW) and river water (RW) were exposed to a solar simulator (lambda: 295-800 nm) and comparative toxicity of propranolol and its degraded mixtures measured using algal (Pseudokirchneriella subcapitata) and rotifer (Brachionus calyciflorus) screening tests. Results suggested a reduction of toxicity in photodegraded mixtures compared to the parent active pharmaceutical ingredient in all samples tested. Chemical analysis of effect test solutions supported the hypothesis that propranolol was transformed into compounds that appear to be less toxic to the organisms tested under the study conditions. Although the reactions were much faster in RW than in DIW, profiles of transformation products were similar in both matrices at two starting concentrations (1 and 10 mg/L). Results for propranolol implied that the reduction of toxicity using algal and rotifer screening tests was probably due to the production of more hydrophilic and more polar transformation products. Such results will provide useful insights into the environmental risk assessment of pharmaceuticals by taking into account their transformation products.