Liquid Chromatographic Methods Combined with Mass Spectrometry in Metabolomics - Proteomic and Metabolomic Approaches to Biomarker Discovery - page 155

In Figure 5 , a typical work ow for metabolic

5. Theodoridis G, Gika HG, Wilson ID. LC-MS-based
methodology for global metabolite pro ling in

metabonomics/metabolomics. Trend Anal Chem 2008;
27

pro ling and data analysis and other work of

the type that would be used in metabolomic/
metabonomic investigations is shown.

:251 e 60.
6. Theodoridis GA, Gika H, Wilson ID. Mass
spectrometry-based holistic analytical approaches for
metabolite pro ling in systems biology studies. Mass

Spectrom Rev 2011;

CONCLUSIONS

. 884-806.
7. Wu Z, Huang Z, Lehmann R, et al. The application of
chromatography-mass

30

spectrometry: methods to

As currently practiced, metabolomic and
metabonomic studies are increasingly being per-
formedusingLC-MS-based techniques. Obtaining
the most comprehensive metabolite pro

:S23 e 32.
8. Wilson ID, Nicholson JK, Castro-Perez J, et al. High
resolution

metabonomics. Chromatographia 2009;

69

liquid chromatography
coupled to oa-TOF mass spectrometry as a tool for
differential metabolic pathway pro

“ ultra performance ”

le does,
however, require the use of more than one separa-
tion mode (e.g., RPLC and HILIC), and more than
one mode of ionization (i.e., both positive and
negative ESI, perhaps with positive and negative
APCI aswell). Although it is clear that themethod-
ology is still rapidly developing, robust protocols
are appearing for various types of sample and
continuing rapid advances in instrumentation
will further improve ef

ling in functional
genomic studies. J Proteome Res 2005; :591 e 8.

9. Plumb RS, Granger JH, Stumpf CL, et al. A rapid
screening approach to metabonomics using UPLC and
oa-TOF mass spectrometry: application to age, gender
and diurnal variation in normal/Zucker obese rats
and black, white and nude mice. Analyst 2005;

4

130 :

844 e 9.
10. Dunn WB, Broadhurst D, Begley P, et al. Procedures for
large-scale metabolic pro ling of serum and plasma

using gas chromatography and liquid chromatography
coupled to mass spectrometry. Nat Protocols 2011;

ciency. The dif culties

that remain center mainly on the identi cation of

unknowns detected as potential biomarkers
during the course of metabolic pro

6 :

1060 e 83.
11. Want EJ, Wilson ID, Gika H, et al. Global metabolic
pro

ling experi-
ments. However, great strides are being made in
the development of metabolite databases and
other resources that will greatly help reduce the
complexity of the task in the future.

ling procedures for urine using UPLC-MS. Nat
Protocols 2010; :1005 e 18.

12 Want EJ, Masson P, Michopoulos F, et al. Global
metabolic pro

5

ling procedures for animal and human
tissues via UPLC-MS. Nature Protocols 2013; :17 e 32.

13. Gika HG, Theodoridis GA, Wingate JE, et al. Within-
day reproducibility of an HPLC-MS-based method
for metabonomic analysis: application to human urine.
J Proteome Res 2007;

8

References
1. Nicholson JK, Connelly J, Lindon JC, et al. Metabo-
nomics: a platform for studying drug toxicity and gene
function. Nat Rev Drug Discov 2002;

:3291 e 3303.
14. Gika HG, Macpherson E, Theodoridis GA, et al. Eval-
uation of the repeatability of ultra-performance liquid
chromatography-TOF-MS for global metabolic pro-

6

:153 e 61.
2. Nicholson JK, Lindon JC. Systems biology: metabo-
nomics. Nature 2008;

1

filing of human urine samples. J Chromatogr B 2009; :

871

:1054 e 6.
3. Plumb RS, Stumpf CL, Gorenstein MV, et al. Metabo-
nomics: the use of electrospray mass spectrometry
coupled to reversed-phase liquid chromatography
shows potential for the screening of rat urine in drug
development. Rapid Commun Mass Spectrom 2002;
2002

455

299 e 305.
15. Michopoulos F, Lai L, Gika H, et al. UPLC-MS-based
analysis of human plasma for metabonomics using
solvent precipitation or solid phase extraction. J Pro-
teome Res 2009; :2114 e 21.

16 Zelena E, Dunn WB, Broadhurst D, et al. Development
of a robust and repeatable UPLC

8

(16):1991 e 6.
4. Plumb RS, Granger J, Stumpf C, et al. Metabonomic
analysis of mouse urine by liquid-chromatography-
time of

MS method for the
long-term metabolomic study of human serum. Anal
Chem 2009; :1357 e 64.

17 Wilson ID, Plumb R, Granger J, et al. HPLC-MS-based
methods for the study of metabonomics. J Chrom B 2005;
817

81

flight mass spectrometry (LC-TOFMS): detec-
tion of strain, diurnal variation and gender differences.
Analyst 2003; :819 e 23.

128 :67 e 76.