title: Reactivity of β-blockers/agonists with aqueous permanganate. Kinetics and transformation products of salbutamol.
abstract: The possible oxidation of two β-blockers, atenolol and propranolol, and one β-agonist, salbutamol, with aqueous potassium permanganate (KMnO4) was investigated by liquid chromatography-quadrupole-time-of-flight-mass spectrometry (LC-QTOF-MS). Under strong oxidation conditions (2 mg L(-1) KMnO4, 24 h), only salbutamol did significantly react. In this way, the oxidation kinetics of salbutamol was further investigated at different concentrations of KMnO4, chloride, phosphate and sample pH by means of a full factorial experimental design. Depending on these factors, half-lives were in the range 1-144 min for drug and it was observed that KMnO4 concentration was the most significant factor, resulting in increased reaction rate as it is increased. Moreover, the reaction of salbutamol is also enhanced at basic pH and to a minor extent by the presence of phosphates, being both factors more relevant at low KMnO4 concentrations. The use of an accurate-mass LC-QTOF-MS system permitted the identification of a total of seven transformation products (TPs). The transformation path of the drug begins by the attack of KMnO4 on two double bonds of the aromatic ring of salbutamol via 3 + 2 and 2 + 2 addition reactions, which resulted in the ring opening and that continues with oxidative reactions to finally produce smaller size TPs, ending with tert-butyl-formamide, as the smallest TP identified. Reaction in real samples showed a slower and partial oxidation of the pharmaceutical, due to other competing water organic constituents, but still exceeding 60%. Moreover, the software predicted toxicity of TPs indicates that they are expected not to be more toxic than salbutamol, in contrast to the results obtained for the predicted toxicity of chlorination TPs, excepting predicted developmental toxicity.
authors.affiliation: Department of Analytical Chemistry, Nutrition and Food Science, IIAA - Institute for Food Analysis and Research, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Tania
authors.initials: T
authors.lastname: Rodríguez-Álvarez
authors.affiliation: Department of Analytical Chemistry, Nutrition and Food Science, IIAA - Institute for Food Analysis and Research, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Rodil
authors.affiliation: Department of Analytical Chemistry, Nutrition and Food Science, IIAA - Institute for Food Analysis and Research, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain. Electronic address: jb.quintana@usc.es.
authors.forename: José Benito
authors.initials: JB
authors.lastname: Quintana
authors.affiliation: Department of Analytical Chemistry, Nutrition and Food Science, IIAA - Institute for Food Analysis and Research, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Cela
mesh_terms: D000318:Adrenergic beta-Agonists / Q000737:chemistry* / Q000633:toxicity; D000319:Adrenergic beta-Antagonists / Q000737:chemistry* / Q000633:toxicity; D000420:Albuterol / Q000737:chemistry* / Q000633:toxicity; D001262:Atenolol / Q000737:chemistry* / Q000633:toxicity; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010084:Oxidation-Reduction; D011196:Potassium Permanganate / Q000737:chemistry*; D011433:Propranolol / Q000737:chemistry* / Q000633:toxicity; D014867:Water / Q000737:chemistry; D014874:Water Pollutants, Chemical / Q000737:chemistry / Q000633:toxicity
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D014874:Water Pollutants, Chemical; D011196:Potassium Permanganate; D014867:Water; D001262:Atenolol; D011433:Propranolol; D000420:Albuterol
keywords: Liquid chromatography-mass spectrometry (LC-MS); Pharmaceuticals; Time-of-flight (TOF); Transformation products; β-agonists; β-blockers