Background The identification of main metabolites and assessment of renal excretion of a novel compound with β-adrenolytic activity (2 RS )-1-(1 H -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
【저자키워드】 mass spectrometry, metabolites, Electrochemistry, Orbitrap, renal clearance, Aminopropan-2-ol compound, 【초록키워드】 Structure, Phase I, lung, in vitro, metabolism, serum, intestine, Urine, in vivo, liver, metabolite, Analysis, Faeces, High-resolution, identification, cytochrome P450, Abstract, kidneys, renal, derivative, API, oxidative, Result, predicted, was done, m/z, metabolised, 【제목키워드】 metabolite,