Daporinad in vitro metabolite profiling via rat, dog, monkey and human liver microsomes by liquid chromatography/quadrupole‐orbitrap mass spectrometry

Daporinad in vitro metabolite profiling via rat, dog, monkey and human liver microsomes by liquid chromatography/quadrupole‐orbitrap mass spectrometry

Rationale Daporinad is a novel and potent inhibitor of nicotinamide phosphoribosyl transferase with potential antineoplastic and antiangiogenic activities. We aimed to explore the metabolites of daporinad generated from liver microsomes and to propose metabolic pathways. Methods The metabolites were...

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Bibliographic Details
Published in:Rapid communications in mass spectrometry Vol. 35; no. 18; pp. e9150 - n/a
Main Authors: Qu, Shan‐Dan, Liu, Guang‐Xuan
Format: Journal Article
Language:English
Published: England Wiley Subscription Services, Inc 30-09-2021
Subjects:
Animals
Antiangiogenics
Biocompatibility
Chromatography
Chromatography, High Pressure Liquid - methods
Dealkylation
Dehydrogenation
Dogs
Haplorhini
Humans
In vivo methods and tests
Ions
Liquid chromatography
Liver
Mass spectrometry
Mass Spectrometry - methods
Metabolites
Microsomes, Liver - chemistry
Monkeys
Nicotinamide
Oxygenation
Positive ions
Quadrupoles
Rats
Scientific imaging
Species Specificity
Spectroscopy
Toxicology
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Summary:Rationale Daporinad is a novel and potent inhibitor of nicotinamide phosphoribosyl transferase with potential antineoplastic and antiangiogenic activities. We aimed to explore the metabolites of daporinad generated from liver microsomes and to propose metabolic pathways. Methods The metabolites were generated by individually incubating daporinad (10 μM) with liver microsomes at 37°C for 60 min. The metabolites were identified by ultra‐high‐performance liquid chromatography/quadrupole‐orbitrap mass spectrometry (UPLC/Q‐Orbitrap‐MS) using electrospray ionization in positive ion mode. They were deduced by accurate MS and MS/MS data. Results In total, 16 metabolites were found and their identities were characterized. In rat, dog and human, they were minor; in monkey, M11 was the most abundant. Daporinad was metabolized mainly through N‐dealkylation, amide hydrolysis, hydrogenation, oxygenation and dehydrogenation. There was no human‐specific metabolite. Conclusions The current study provided an overview of the metabolism of daporinad, which is helpful in predicting in vivo metabolites and in selecting animal species for toxicology studies.
ISSN:0951-4198
1097-0231
DOI:10.1002/rcm.9150