title: Structural Characterization of Anticancer Drug Paclitaxel  and Its Metabolites Using Ion Mobility Mass Spectrometry  and Tandem Mass Spectrometry.
abstract: Paclitaxel (PTX) is a popular anticancer drug used in the treatment of various types of cancers. PTX is metabolized in the human liver by cytochrome P450 to two structural isomers, 3′-p-hydroxypaclitaxel (3p-OHP) and 6α-hydroxypaclitaxel (6α-OHP). Analyzing PTX and its two metabolites, 3p-OHP and 6α-OHP, is crucial for understanding general pharmacokinetics, drug activity, and drug resistance. In this study, electrospray ionization ion mobility mass spectrometry (ESI-IM-MS) and collision induced dissociation (CID) are utilized for the identification and characterization of PTX and its metabolites. Ion mobility distributions of 3p-OHP and 6α-OHP indicate that hydroxylation of PTX at different sites yields distinct gas phase structures. Addition of monovalent alkali metal and silver metal cations enhances the distinct dissociation patterns of these structural isomers. The differences observed in the CID patterns of metalated PTX and its two metabolites are investigated further by evaluating their gas-phase structures. Density functional theory calculations suggest that the observed structural changes and dissociation pathways are the result of the interactions between the metal cation and the hydroxyl substituents in PTX metabolites.
authors.affiliation: Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 790-784, Korea
authors.forename: Hong Hee
authors.initials: HH
authors.lastname: Lee
authors.forename: Areum
authors.initials: A
authors.lastname: Hong
authors.forename: Yunju
authors.initials: Y
authors.lastname: Cho
authors.forename: Sunghwan
authors.initials: S
authors.lastname: Kim
authors.forename: Won Jong
authors.initials: WJ
authors.lastname: Kim
authors.forename: Hugh I
authors.initials: HI
authors.lastname: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D002412:Cations / Q000737:chemistry; D005740:Gases / Q000737:chemistry; D006900:Hydroxylation; D008670:Metals / Q000737:chemistry; D008956:Models, Chemical; D017239:Paclitaxel / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D043823:Taxoids / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002412:Cations; D005740:Gases; D008670:Metals; D043823:Taxoids; C102050:3'-p-hydroxypaclitaxel; C086219:6-hydroxytaxol; D017239:Paclitaxel