title: The development of the LC-MS/MS method based on S-9 biotransformation for detection of metabolites of selected β-adrenolytics in surface water.
abstract: Pharmaceuticals consumption in Poland is high. One of the most frequently prescribed is cardiovascular drugs. Due to their relatively high hydrophilic properties, they are not completely eliminated during wastewater treatment processes. In contrast to parent compounds, the presence of cardiovascular metabolites is rarely investigated in surface waters. The goal of this paper was to develop the methodology for detection of metabolites of selected beta-blockers: metoprolol, bisoprolol and propranolol. These metabolites were obtained by the incubation of parent compounds with S9 rat's liver fraction and used for the development and optimization of the low resolution LC-MS/MS method. Accurate mass spectrometry measurements were applied for validation of this method. The incubation of the parent compound with S9 fraction resulted only in propranolol's metabolites generation. However, on the basis of hydroxypropranolol, theoretically transitions for mono- and dihydroxy-metoprolol and bisoprolol derivatives were generated for MRM mode and applied for surface water analysis. The analysis revealed the presence of some of the target metabolites in the Vistula river. This work is the first one proposing the application of biotrasformation in the methodology of low resolution LC-MS-MS analysis of metabolites of cardiovascular drugs in surface water.
authors: Department of Bioanalysis and Drugs Analysis, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, Warsaw PL-02097, Poland.
authors: Albert
authors: A
authors: Stankiewicz
authors: Department of Bioanalysis and Drugs Analysis, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, Warsaw PL-02097, Poland. Electronic address: joanna.giebultowicz@wum.edu.pl.
authors: Joanna
authors: J
authors: Giebułtowicz
authors: Department of Environmental Health Sciences, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, Warsaw PL-02097, Poland.
authors: Marcin
authors: M
authors: Stefański
authors: Department of Environmental Health Sciences, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, Warsaw PL-02097, Poland.
authors: Katarzyna
authors: K
authors: Sikorska
authors: Department of Bioanalysis and Drugs Analysis, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, Warsaw PL-02097, Poland.
authors: Piotr
authors: P
authors: Wroczyński
authors: Department of Environmental Health Sciences, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, Warsaw PL-02097, Poland.
authors: Grzegorz
authors: G
authors: Nałęcz-Jawecki
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D017298:Bisoprolol / Q000378:metabolism*; D002853:Chromatography, Liquid; D008099:Liver / Q000378:metabolism*; D008297:Male; D008790:Metoprolol / Q000378:metabolism*; D011044:Poland; D011433:Propranolol / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D045483:Rivers; D053719:Tandem Mass Spectrometry; D014865:Waste Disposal, Fluid; D014874:Water Pollutants, Chemical / Q000378:metabolism*
chemical_list: D000319:Adrenergic beta-Antagonists; D014874:Water Pollutants, Chemical; D011433:Propranolol; D008790:Metoprolol; D017298:Bisoprolol
keywords: Bisoprolol; Metabolites; Metoprolol; Propranolol; Surface water; β-Adrenolitic