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Phosphonium labeling for increasing metabolomic coverage of neutral lipids using electrospray ionization mass spectrometry
Authors:Hin‐Koon Woo  Eden P Go  Linh Hoang  Sunia A Trauger  Benjamin Bowen  Gary Siuzdak  Trent R Northen
Institution:1. Department of Molecular Biology, Scripps Center for Mass Spectrometry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA;2. Harrington Department of Bioengineering, Arizona State University, PO Box 879709, Tempe, AZ 85287, USA;3. Department of GTL Bioenergy and Structural Biology, Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA
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. Published in 2009 by John Wiley & Sons, Ltd.
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