Phosphonium labeling for increasing metabolomic coverage of neutral lipids using electrospray ionization mass spectrometry.
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.
Woo
Hin-Koon
HK
Department of Molecular Biology, Scripps Center for Mass Spectrometry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Go
Eden P
EP
Hoang
Linh
L
Trauger
Sunia A
SA
Bowen
Benjamin
B
Siuzdak
Gary
G
Northen
Trent R
TR
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
D008055:Lipids; D009943:Organophosphorus Compounds; C405845:tris(trimethoxyphenyl)phosphonium acetyl