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In vivo metabolite identification of acotiamide in rats using ultra‐performance liquid chromatography–quadrupole/time‐of‐flight mass spectrometry
Author(s) -
Patel Prinesh N.,
Kalariya Pradipbhai D.,
Thummar Mohit,
Gananadhamu S.,
Srinivas R.
Publication year - 2017
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.3915
Subject(s) - chemistry , chromatography , metabolite , protein precipitation , in vivo , mass spectrometry , electrospray ionization , pharmacokinetics , solid phase extraction , glucuronide , tandem mass spectrometry , liquid chromatography–mass spectrometry , pharmacology , biochemistry , medicine , microbiology and biotechnology , biology
Acotiamide hydrochloride (ACT) is a drug used for the treatment of functional dyspepsia. Understanding which metabolites are likely to be formed in vivo is essential for interpreting pharmacology, pharmacokinetic and toxicology data. The metabolism of ACT has been investigated using a specific and sensitive liquid chromatography positive ion electrospray ionization high‐resolution tandem mass spectrometry method. In vivo samples including rat plasma, urine and feces were collected separately after dosing healthy Sprague–Dawley rats at a dose of 20 mg kg −1 ACT at different time points up to 24 h. The metabolites were enriched by optimized sample preparation involving protein precipitation using acetonitrile followed by solid‐phase extraction. The mass defect filter technique was used for better detection of both predicted and unexpected drug metabolites with the majority of interference ions removed. The structural elucidation of the metabolites was performed by comparing their [M + H] + ions and their product ions with those of the parent drug. As a result, a total of seven hitherto unknown metabolites were characterized from the biosamples. The only phase I metabolite detected was N‐ despropyl acotiamide, whereas six phase II glucuronide conjugate metabolites were identified.