title: Identification of metabolites of fluorine-18-labeled M2 muscarinic receptor agonist, 3-(3-[(3-fluoropropyl)thio]-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine, produced by human and rat hepatocytes.
abstract: An accurate, rapid method for the determination of unmetabolized 3-(3-[(3-[18F]fluoropropyl)thio]-1,2,5-thiadiazol-4-yl)-1.2,5,6-tetrahydro-1-methylpyridine (FP-TZTP), a selective M2 muscarinic agonist, is necessary in order to obtain quantitative information from positron emission tomography (PET) imaging. Using LC-MS-MS to analyze products from cultured human and rat hepatocytes, we identified metabolites resulting from oxidation of the nitrogen in the tetrahydropyridine ring, sulfur-oxidation, demethylation of the tertiary amine, and oxidation of the tetrahydropyridine ring. From the knowledge of the structure of the metabolites, we have developed a two-step extraction sequence that allows rapid determination of the parent fraction in plasma without time-consuming chromatographic analysis.
authors.affiliation: PET Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. yma@mail.cc.nih.gov
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.forename: Dale O
authors.initials: DO
authors.lastname: Kiesewetter
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Jagoda
authors.forename: Bill X
authors.initials: BX
authors.lastname: Huang
authors.forename: William C
authors.initials: WC
authors.lastname: Eckelman
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005461:Fluorine / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D018721:Muscarinic Agonists / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000378:metabolism*; D014055:Tomography, Emission-Computed
chemical_list: D018721:Muscarinic Agonists; D011725:Pyridines; D013844:Thiazoles; D005461:Fluorine; C115177:FP-TZTP