title: Structural elucidation of in vivo metabolites of phencynonate and its analogue thiencynonate in rats by HPLC-ESI-MSn.
abstract: The structural elucidation of the metabolites of phencynonate and its analogue thiencynonate in rats was performed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS(n)) in positive ion mode, by comparing their changes in molecular masses (DeltaM), retention times and spectral patterns with those of the parent drug. Phencynonate and thiencynonate were easily biotransformed in vivo by the pathways of N-demethylated, oxidative, hydroxylated and methoxylated to form seventeen metabolites that retained the some features of the two parent molecules. These metabolites included ten phencynonate metabolites (N-demethyphencynonate monoxide, N-demethyhydroxy phencynonate, phencynonate monoxide, hydroxyphencynonate, phencynonate dioxide, methoxyphencynonate, dihydroxyphencynonate, dihydroxyphencynonate, hydroxymethoxy phencynonate, trihydroxyphencynonate) and seven thiencynonate metabolites (N-demethy thiencynonate, N-demethythiencynonate monoxide, N-demethyhydroxythiencynonate, thiencynonate monoxide, hydroxythiencynonate, hydroxythiencynonate monoxide, dihydroxy thiencynonate). The described method has wide applicability to rapidly screen and provide structural information of these metabolites. The identifications of precise structures of these metabolites need to be confirmed by other techniques such as the (1)H and (13)C NMR.
authors.affiliation: Department of Pharmacology, School of Chemical Biology & Pharmaceutical Sciences, Capital Medical University, Youanmen, Beijing 100069, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Yuyin
authors.initials: Y
authors.lastname: Kou
authors.forename: Ming
authors.initials: M
authors.lastname: Xue
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Xu
authors.forename: Liu
authors.initials: L
authors.lastname: He
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Ruan
authors.forename: Keliang
authors.initials: K
authors.lastname: Liu
mesh_terms: D000818:Animals; D001372:Aza Compounds / Q000737:chemistry* / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006016:Glycolates / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013876:Thiophenes / Q000737:chemistry* / Q000378:metabolism
chemical_list: C504860:3-methyl-3-azabicyclo(3,3,1)nonanyl-9-alpha-yl-alpha-cyclopentyl-alpha-phenyl-alpha-glycolate; D001372:Aza Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006016:Glycolates; C516245:N-methyl-9-(3-azabicyclo(3.3.1)nonanyl)-2'-cyclopentyl-2'-hydroxy-2'-thienylacetate; D013876:Thiophenes