title: In vivo metabolite identification of acotiamide in rats using ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry.
abstract: 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-1ACT 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.
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.
authors.forename: Prinesh N
authors.initials: PN
authors.lastname: Patel
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.
authors.forename: Pradipbhai D
authors.initials: PD
authors.lastname: Kalariya
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.
authors.forename: Mohit
authors.initials: M
authors.lastname: Thummar
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.
authors.forename: S
authors.initials: S
authors.lastname: Gananadhamu
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.|National Centre for Mass Spectrometry, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, India.
authors.forename: R
authors.initials: R
authors.lastname: Srinivas
mesh_terms: D000818:Animals; D001549:Benzamides / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013844:Thiazoles / Q000378:metabolism*
chemical_list: D001549:Benzamides; D013844:Thiazoles; C410959:Z 338
keywords: LC-QTOF-MS; acotiamide; in vivo metabolites; mass defect filter; metabolite identification