title: Phosphonium labeling for increasing metabolomic coverage of neutral lipids using electrospray ionization mass spectrometry.
abstract: Mass spectrometry has become an indispensable tool for the global study of metabolites (metabolomics), primarily using electrospray ionization mass spectrometry (ESI-MS). However, many important classes of molecules such as neutral lipids do not ionize well by ESI and go undetected. Chemical derivatization of metabolites can enhance ionization for increased sensitivity and metabolomic coverage. Here we describe the use of tris(2,4,6,-trimethoxyphenyl)phosphonium acetic acid (TMPP-AA) to improve liquid chromatography (LC)/ESI-MS detection of hydroxylated metabolites (i.e. lipids) from serum extracts. Cholesterol which is not normally detected from serum using ESI is observed with attomole sensitivity. This approach was applied to identify four endogenous lipids (hexadecanoyl-sn-glycerol, dihydrotachysterol, octadecanol, and alpha-tocopherol) from human serum. Overall, this approach extends the types of metabolites which can be detected using standard ESI-MS instrumentation and demonstrates the potential for targeted metabolomics analysis.
authors.affiliation: Department of Molecular Biology, Scripps Center for Mass Spectrometry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Hin-Koon
authors.initials: HK
authors.lastname: Woo
authors.forename: Eden P
authors.initials: EP
authors.lastname: Go
authors.forename: Linh
authors.initials: L
authors.lastname: Hoang
authors.forename: Sunia A
authors.initials: SA
authors.lastname: Trauger
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bowen
authors.forename: Gary
authors.initials: G
authors.lastname: Siuzdak
authors.forename: Trent R
authors.initials: TR
authors.lastname: Northen
mesh_terms: D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood / Q000737:chemistry*; D008297:Male; D055432:Metabolomics; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013194:Staining and Labeling
chemical_list: D008055:Lipids; D009943:Organophosphorus Compounds; C405845:tris(trimethoxyphenyl)phosphonium acetyl