Kinetics and degradation products for direct photolysis of beta-blockers in water.
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.
Liu
Qin-Tao
QT
AstraZeneca UK Ltd. Global Safety Health and Environment, Brixham Environmental Laboratory, Brixham, Devon, UK. Qintao.Liu@astrazeneca.com
Williams
Helen E
HE
D000319:Adrenergic beta-Antagonists / Q000032:analysis / Q000378:metabolism*; D001262:Atenolol / Q000032:analysis / Q000378:metabolism; D001673:Biodegradation, Environmental; D002851:Chromatography, High Pressure Liquid; D016166:Free Radical Scavengers / Q000737:chemistry; D005618:Fresh Water; D007220:Industrial Waste; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008790:Metoprolol / Q000032:analysis / Q000378:metabolism; D010084:Oxidation-Reduction; D010782:Photolysis; D011433:Propranolol / Q000032:analysis / Q000378:metabolism; D012621:Seasons; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D016166:Free Radical Scavengers; D007220:Industrial Waste; D014874:Water Pollutants, Chemical; D001262:Atenolol; D011433:Propranolol; D008790:Metoprolol