TY - JOUR
T1 - Analytical strategies for LC-MS-based targeted metabolomics
AU - Lu, Wenyun
AU - Bennett, Bryson D.
AU - Rabinowitz, Joshua D.
N1 - Funding Information:
This research was supported by NIH grant GM071508 for Center of Quantitative Biology at Princeton University. Additional support came from Beckman Foundation, NSF DDDAS grant CNS-0540181, American Heart Association grant 0635188N, NSF Career Award MCB-0643859, and NIH grant AI078063 (to J.D.R.). We thank Kathleen Anderson and Josef Ruzicka from Thermo Fisher Scientific, Bob Walker and Jim Lau from Agilent, and James A. Ferguson from AppliedBiosystems for analyses of selected samples, and Mark Sanders and the reviewers for comments on the manuscript.
PY - 2008/8/15
Y1 - 2008/8/15
N2 - Recent advances in mass spectrometry are enabling improved analysis of endogenous metabolites. Here we discuss several issues relevant to developing liquid chromatography-electrospray ionization-mass spectrometry methods for targeted metabolomics (i.e., quantitative analysis of dozens to hundreds of specific metabolites). Sample preparation and liquid chromatography approaches are discussed, with an eye towards the challenge of dealing with a diversity of metabolite classes in parallel. Evidence is presented that heated electrospray ionization (ESI) generally gives improved signal compared to the more traditional unheated ESI. Applicability to targeted metabolomics of triple quadrupole mass spectrometry operating in multiple reaction monitoring (MRM) mode and high mass resolution full scan mass spectrometry (e.g., time-of-flight, Orbitrap) are described. We suggest that both are viable solutions, with MRM preferred when targeting a more limited number of analytes, and full scan preferred for its potential ability to bridge targeted and untargeted metabolomics.
AB - Recent advances in mass spectrometry are enabling improved analysis of endogenous metabolites. Here we discuss several issues relevant to developing liquid chromatography-electrospray ionization-mass spectrometry methods for targeted metabolomics (i.e., quantitative analysis of dozens to hundreds of specific metabolites). Sample preparation and liquid chromatography approaches are discussed, with an eye towards the challenge of dealing with a diversity of metabolite classes in parallel. Evidence is presented that heated electrospray ionization (ESI) generally gives improved signal compared to the more traditional unheated ESI. Applicability to targeted metabolomics of triple quadrupole mass spectrometry operating in multiple reaction monitoring (MRM) mode and high mass resolution full scan mass spectrometry (e.g., time-of-flight, Orbitrap) are described. We suggest that both are viable solutions, with MRM preferred when targeting a more limited number of analytes, and full scan preferred for its potential ability to bridge targeted and untargeted metabolomics.
KW - Full scan
KW - Heated electrospray ionization
KW - Hydrophilic interaction chromatography (HILIC)
KW - Ion-pairing chromatography
KW - Liquid chromatography
KW - Mass spectrometry
KW - Multiple reaction monitoring (MRM)
KW - Targeted metabolomics
KW - Time-of-flight
KW - Triple quadrupole
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U2 - 10.1016/j.jchromb.2008.04.031
DO - 10.1016/j.jchromb.2008.04.031
M3 - Article
C2 - 18502704
AN - SCOPUS:48749132804
SN - 1570-0232
VL - 871
SP - 236
EP - 242
JO - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
JF - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
IS - 2
ER -