A preliminary metabolites identification of a novel compound with β-adrenolytic activity
In: Pharmacol Rep, 2021
academicJournal
Zugriff:
BACKGROUND: The identification of main metabolites and assessment of renal excretion of a novel compound with β-adrenolytic activity (2RS)-1-(1H-indol-4-yloxy)-3-((2-(2-methoxyphenoxy)ethyl)amino)propan-2-ol, briefly called (RS)-9 or 2F109, were studied in vivo in rat serum, urine, faeces, liver, intestine, lungs and kidneys, and in vitro in rat liver microsomes. METHODS: Structures of the metabolites have been developed by comparing the high-resolution product ion mass spectra of metabolites and the parent compound based on the differences in mass values of main fragments. Quantitative analysis of (RS)-9 was done using a system of liquid chromatography coupled with a triple quadrupole mass spectrometer API 2000. Identification studies of predicted metabolites were made by a high-resolution mass spectrometer LTQ XL Orbitrap Discovery and using a Roxy(™) system, for online electrochemical mimicry of oxidative metabolism by cytochrome P450s connected to QTRAP 5500. RESULTS: For (RS)-9 (m/z 357.2084) phase I metabolites derived from oxidation process: hydroxyl derivatives (m/z 373.2470) and dihydroxyl derivatives (m/z 389.4318), and phase II metabolites: N-methylated compound (m/z 371.1612), O-glucuronide (m/z 533.5118), and sulfate (m/z 437.2350) were identified. CONCLUSION: (RS)-9 was extensively metabolised to several phase I and II metabolites, and renal excretion was a minor route in its elimination. GRAPHIC ABSTRACT: [Image: see text]
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A preliminary metabolites identification of a novel compound with β-adrenolytic activity
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Autor/in / Beteiligte Person: | Walczak, Maria ; Suraj-Prażmowska, Joanna ; Kuś, Kamil ; Kij, Agnieszka ; Groszek, Grażyna |
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Zeitschrift: | Pharmacol Rep, 2021 |
Veröffentlichung: | Springer International Publishing, 2021 |
Medientyp: | academicJournal |
DOI: | 10.1007/s43440-021-00273-9 |
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