title: Distinct Fragmentation Pathways of Anticancer Drugs Induced by Charge-Carrying Cations in the Gas Phase.
abstract: With the growth of the pharmaceutical industry, structural elucidation of drugs and derivatives using tandem mass spectrometry (MS2) has become essential for drug development and pharmacokinetics studies because of its high sensitivity and low sample requirement. Thus, research seeking to understand fundamental relationships between fragmentation patterns and precursor ion structures in the gas phase has gained attention. In this study, we investigate the fragmentation of the widely used anticancer drugs, doxorubicin (DOX), vinblastine (VBL), and vinorelbine (VRL), complexed by a singly charged proton or alkali metal ion (Li+, Na+, K+) in the gas phase. The drug-cation complexes exhibit distinct fragmentation patterns in tandem mass spectra as a function of cation size. The trends in fragmentation patterns are explicable in terms of structures derived from ion mobility mass spectrometry (IM-MS) and theoretical calculations. Graphical Abstract ᅟ.
authors.affiliation: Department of Chemistry, Research Institute for Natural Sciences, Korea University, Seoul, 02841, Republic of Korea.|Division of Metrology for Quality of Life, Korea Research Institute of Standards and Science, Daejeon, 34113, Republic of Korea.
authors.forename: Areum
authors.initials: A
authors.lastname: Hong
authors.affiliation: Division of Metrology for Quality of Life, Korea Research Institute of Standards and Science, Daejeon, 34113, Republic of Korea.
authors.forename: Hong Hee
authors.initials: HH
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Research Institute for Natural Sciences, Korea University, Seoul, 02841, Republic of Korea.
authors.forename: Chae Eun
authors.initials: CE
authors.lastname: Heo
authors.affiliation: Green-Nano Materials Research Center, Daegu, 41566, Republic of Korea.
authors.forename: Yunju
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Green-Nano Materials Research Center, Daegu, 41566, Republic of Korea.|Department of Chemistry, Kyungpook National University, Daegu, 41566, Republic of Korea.
authors.forename: Sunghwan
authors.initials: S
authors.lastname: Kim
authors.affiliation: Division of Metrology for Quality of Life, Korea Research Institute of Standards and Science, Daejeon, 34113, Republic of Korea.
authors.forename: Dukjin
authors.initials: D
authors.lastname: Kang
authors.affiliation: Department of Chemistry, Research Institute for Natural Sciences, Korea University, Seoul, 02841, Republic of Korea. hughkim@korea.ac.kr.
authors.forename: Hugh I
authors.initials: HI
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002412:Cations / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry*; D005740:Gases / Q000737:chemistry; D000075663:Ion Mobility Spectrometry / Q000379:methods; D008672:Metals, Alkali / Q000737:chemistry; D008958:Models, Molecular; D011522:Protons; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014747:Vinblastine / Q000737:chemistry*; D000077235:Vinorelbine / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D005740:Gases; D008672:Metals, Alkali; D011522:Protons; D014747:Vinblastine; D004317:Doxorubicin; D000077235:Vinorelbine
keywords: Alkali metal; Anticancer drug; Doxorubicin; Fragmentation; Ion mobility mass spectrometry; Proton; Structural elucidation; Tandem mass spectrometry; Theoretical calculation; Vinblastine; Vinorelbine