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instrumentation platforms formetabolic pro
ling
and biomarker discovery. One could argue that
the NMR spectrometer actually has very high
detection sensitivity considering the fact that it
is detecting a negligible fraction of the nuclei in
the sample. The NMR signal is directly propor-
tional to the population difference between the
two energy states for spin-½ nuclei. The Boltz-
mann distribution gives the relative populations
between the low and high energy levels, and the
population difference is extremely small. At 500
MHz, only about 1 out of every 10,000 nuclei
contributes to the detected NMR signal.
Although it is true that currently NMR spec-
troscopy is hard pressed to detect subnanomolar
concentration of metabolites without the use of
high
based metabonomics for large-scale epidemiological
research: the INTERMAP study. Anal Chem 2006;
78
:
2199
e
208.
2. Keun HC, Ebbels TMD, Antti H, et al. Analytical
reproducibility in
1
H NMR-based metabonomic
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6.
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unveiled by NMR spectroscopy of human bio
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4.
Iles RA. Nuclear magnetic resonance spectroscopy
and genetic disorders. Curr Med Chem 2008;
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5. Coen M, Holmes E, Lindon JC, et al. NMR-based
metabolic pro
ling and metabonomic approaches to
problems in molecular toxicology. Chem Res Toxicol
2008;
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27.
6. Kolokolova TN, Savel
21
ev OY, Sergeev NM. Metabolic
analysis of human biological
'
1
H NMR
fluids by
:104
e
20.
7. Gowda GAN, Zhang SC, Gu HW, et al. Metabolomics-
based methods for early disease diagnostics. Expert
Rev Mol Diagn 2008;
spectroscopy. J Anal Chem 2008;
63
field spectrometers, whereas mass spec-
trometry has detection limits in the femto range,
NMR is both noninvasive and nondestructive
and has great potential for clinical applications.
A growing number of groups have been trying
to increase the population polarization to boost
sensitivity: CIDNP (chemically induced dynamic
nuclear polarization),
189
Optical Pumping of
129
Xe via SPINOE (spin polarization
e
induced
nuclear Overhauser enhancement),
190
PHIP
(parahydrogen-induced polarization),
191
and
DNP (dynamic nuclear polarization).
192,193
Of
these methods, DNP has particularly taken off
in recent years, as researchers have discovered
ways to apply it to liquid-state, HR-MAS, and
in vivo work. DNP, in conjunction with nontradi-
tional and extremely fast multidimensional NMR
experiments under development (ultrafast
methods) whereby a 2D spectrum can be
collected within approximately 0.1 s on a 200
nM (nanomolar) sample, can perhaps someday
rival mass spectroscopy
:617
e
33.
8. Xu EY, Schaefer WH, Xu QW. Metabolomics in
pharmaceutical research and development: metabo-
lites, mechanisms and pathways. Curr Opin Drug DI
DE 2009;
8
:40
e
52.
9. Wishart DS. Quantitative metabolomics using NMR.
Trac-Trends in Anal Chem 2008;
12
:228
e
37.
10. Bictash M, Ebbels TM, Chan Q, et al. Opening up the
“
27
: metabolic phenotyping and metabolome-
wide association studies in epidemiology. J Clin Epi-
demiol 2010;
black box
”
:970
e
9.
11. Bernini P, Bertini I, Luchinat C, et al. Individual
human phenotypes in metabolic space and time.
J Proteome Res 2009;
63
:4264
e
71.
12. Nicholson G, Rantalainen M, Maher AD, et al.
Human metabolic pro
8
les are stably controlled by
genetic and environmental variation. Mol Sys Biol
2011;
:525.
13. Bollard ME, Stanley EG, Lindon JC, et al. NMR-based
metabonomic approaches for evaluating physiological
in
7
uences on bio
uid composition. NMR Biomed 2005;
:143
e
62.
14. Slupsky CM, Rankin KN, Wagner J, et al. Investiga-
tions of the effects of gender, diurnal variation, and
age in human urinary metabolomic pro
18
s high sensitivity while
retaining all of its strength in analytical reproduc-
ibility and quantitativeness.
194,195
'
les. Anal
:6995
e
7004.
15. Keeler J. Understanding NMR Spectroscopy. 2nd ed.
Chichester: John Wiley and Sons; 2010.
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References
1. Dumas ME, Maibaum EC, Teague C, et al. Assessment
of analytical reproducibility of
1
H NMR spectroscopy
16.
Jacobsen N. NMR Spectroscopy Explained: Simpli
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Theory, Applications and Examples for Organic Chemistry
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