title: Localization of fatty acyl and double bond positions in phosphatidylcholines using a dual stage CID fragmentation coupled with ion mobility mass spectrometry.
abstract: A high content molecular fragmentation for the analysis of phosphatidylcholines (PC) was achieved utilizing a two-stage [trap (first generation fragmentation) and transfer (second generation fragmentation)] collision-induced dissociation (CID) in combination with travelling-wave ion mobility spectrometry (TWIMS). The novel aspects of this work reside in the fact that a TWIMS arrangement was used to obtain a high level structural information including location of fatty acyl substituents and double bonds for PCs in plasma, and the presence of alkali metal adduct ions such as [M + Li](+) was not required to obtain double bond positions. Elemental compositions for fragment ions were confirmed by accurate mass measurements. A very specific first generation fragment ion m/z 577 (M-phosphoryl choline) from the PC [16:0/18:1 (9Z)] was produced, which by further CID generated acylium ions containing either the fatty acyl 16:0 (C(15)H(31)CO(+), m/z 239) or 18:1 (9Z) (C(17)H(33)CO(+), m/z 265) substituent. Subsequent water loss from these acylium ions was key in producing hydrocarbon fragment ions mainly from the α-proximal position of the carbonyl group such as the hydrocarbon ion m/z 67 (+H(2)C-HC = CH-CH = CH(2)). Formation of these ions was of important significance for determining double bonds in the fatty acyl chains. In addition to this, and with the aid of (13)C labeled lyso-phosphatidylcholine (LPC) 18:1 (9Z) in the ω-position (methyl) TAP fragmentation produced the ion at m/z 57. And was proven to be derived from the α-proximal (carboxylate) or distant ω-position (methyl) in the LPC.
authors.affiliation: Department of Atherosclerosis Exploratory Biomarkers, Merck Research Laboratories, 126 E. Lincoln Ave, 80Y-2D7, Rahway, NJ 07065, USA. jose_castro-perez@merck.com
authors.forename: Jose
authors.initials: J
authors.lastname: Castro-Perez
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Roddy
authors.forename: Nico M M
authors.initials: NM
authors.lastname: Nibbering
authors.forename: Vinit
authors.initials: V
authors.lastname: Shah
authors.forename: David G
authors.initials: DG
authors.lastname: McLaren
authors.forename: Stephen
authors.initials: S
authors.lastname: Previs
authors.forename: Athula B
authors.initials: AB
authors.lastname: Attygalle
authors.forename: Kithsiri
authors.initials: K
authors.lastname: Herath
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.forename: Sheng-Ping
authors.initials: SP
authors.lastname: Wang
authors.forename: Lyndon
authors.initials: L
authors.lastname: Mitnaul
authors.forename: Brian K
authors.initials: BK
authors.lastname: Hubbard
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Vreeken
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Johns
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankemeier
mesh_terms: D000818:Animals; D002518:Ceramides / Q000097:blood / Q000737:chemistry; D007477:Ions / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D008970:Molecular Weight; D010713:Phosphatidylcholines / Q000097:blood / Q000737:chemistry*; D010743:Phospholipids / Q000097:blood / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013109:Sphingomyelins / Q000097:blood / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D002518:Ceramides; D007477:Ions; D010713:Phosphatidylcholines; D010743:Phospholipids; D013109:Sphingomyelins; D014867:Water