1Department of Chemistry and Biochemistry, Eastern Washington University, USA
2Forensic Toxicology Drug Testing Laboratory, Tripler Army Medical Center, USA
*Corresponding author:
Wes E Steiner
Department of Chemistry and Biochemistry
Eastern Washington University, 226 science Building
Cheney, WA 99004, USA
Tel: 509-359-6521
Fax: 509-359-6973
E-mail: wsteiner@ewu.edu
Received August 01, 2012; Accepted August 06, 2012; Published August 10,
2012
Citation:Steiner WE, English WA (2012) Emerging Trends in Liquid Chromatography
and Mass Spectrometry Instrumentation for Analytical & Bioanalytical
Techniques. J Anal Bioanal Tech 3:e106. doi:10.4172/2155-9872.1000e106
With recent advancement in instrumentation from a variety of
researchers and manufactures the use of liquid chromatography (LC)
and mass spectrometry (MS) has become a powerful twodimensional
(2D) hyphenated technology for the use in a wide assortment of
analytical and bioanalytical techniques for the analysis of nucleic
acids, amino acids, peptides, proteins, carbohydrates, lipids, and
etcetera [1-3] and/or in the main classification of omics fields such
as genomics, proteomics, metabolomics, lipidomics, and etcetera [4-7]. This advancement in LCMS was originally and still is fueled by
the need for more powerful analytical and bioanalytical techniques
that can accurately and precisely discriminate target analytes from
high complexity mixtures in a sensitive and selective way. With this
in mind, this review will briefly attempt to focus on the most current
classifications and emerging trends in LC-MS instrumentation and
their respective contributions to the field of analytical and bioanalytical
techniques.
Two primary classifications in the use of LC-MS come to mind
in the form of discovery and directed analysis of complex samples.
With discovery LC-MS taking the form of qualitative types of assays
employing ultra performance liquid chromatography (UPLC) coupled
to a variety of mass spectrometers that include for example time-offlight,
quadrupole-ion trap, linear-ion trap, Fourier transform ion
cyclotron resonance, and orbi-ion trap mass spectrometers (i.e.,
TOFMS, QITMS, LITMS, FT-ICRMS, Orbi-ITMS respectively) [8-10],
and directed LC-MS taking the form of quantitative types of assays that
employ UPLC coupled to mass spectrometers that typically utilize timeof-
flight, single quadrupole, and triple quadrupole mass spectrometers
(i.e., TOFMS, QMS, QqQMS) [11-13]. These two distinct classifications
have now recently become blurred with the emergence of a new
hybrid class of LC-MS instrumentation that has the unique ability to
do both routine qualitative discovery as well as routine quantitative
directed analysis of high complexity mixtures. This hybrid class of LCMS
instrumentation typically takes the form of an UPLC separation
system interfaced to two or more mass spectrometers that are placed in
series such as a UPLC-QMS/TOFMS, UPLC-QITMS/TOFMS, UPLC
QqQMS/TOFMS, or UPLC-QqQMS/LITMS system [9,10,14,15].
The combination of this hybrid class of LC-MS to do both routine
qualitative discovery and quantitative directed analysis of complex
mixtures is perhaps one of the most significant combinations of
developments in separations and mass spectrometry detection science
for analytical & bioanalytical techniques in the past decade. Take for
example traditional low pressure (e.g., 400 bar) long length column
(e.g. 10-25 cm) high performance liquid chromatography (HPLC) in
comparison to higher pressure (e.g., 1200 bar) shorter length column
(e.g., 1.0 - 1.2 cm) UPLC separations which now allows for rapid
injection cycles, a 10-20 times reduction in delay volumes, decreased
sample broadening, increased sample throughput, and reduced
carryover. This in turn translates into increased resolution of larger
peak capacities that will enhance mass spectrometry sensitivity while
still extending the dynamic range of mass spectrometry to yield faster
and more consistent results. Thus, giving the researcher an increased level of robustness and reliability out of their LC systems and improved
detection capabilities when paired with a MS system [16,17].
Thus, when paring for example a hybrid MS system (i.e., QqQMS/
TOFMS), with that of an UPLC system as discussed above, the serial
stacking of two typically independent MS instruments provides a
uniquely integrated qualitative discovery and quantitative directed
analysis workflow into a single platform that truly helps to define the
whole as being more than the sum of its parts. Here the front ends of
this example hybrid MS employs a QqQMS that enables comprehensive
quantitative precursor to product ion transitions for most components
in high complexity mixtures. With sensitivity and precision that is now
becoming almost comparable to that of traditional high-performance
standalone QqQMS systems. The back end of this example hybrid MS
employs a TOFMS that delivers rapid acquisition speeds up to 100
spectra per second, a high level of sample peak resolution of up to
40,000 FWHM, and a high level of sensitivity with a mass accuracy of ≤
2 ppm for both precursor and product ion scan modes. These TOFMS
attributes, with emphasis on accurate mass determinations, allows for
the effective qualitative analysis of high complexity mixtures. To that
end, when the combination of the QqQMS with that of a TOFMS takes
place to form a QqQMS/TOFMS instrument current researchers are
able to utilize one of the most rapid, sensitive, high-resolution hybrid
MS currently available to do both qualitative discovery and quantitative
directed analysis at the same time [2,9,18].
In closing, as we look to the future of LC-MS instrumentation
for the analysis of high complexity samples for analytical &
bioanalytical techniques we feel confident this new hybrid class of
LC-MS instrumentation that has the unique ability to do both routine
qualitative discovery and routine quantitative directed analysis of high
complexity samples may well in fact phase out the traditional class of
standalone LC-MS instrumentation that is typically found in present
laboratories today. The ability to combine discovery and directed analysis
into one instrument alone is not just the cost effective replacement of
two standalone instruments with one, but rather the multiplying effect
of the amount of qualitative and quantitative information obtained by
the researcher in a single temporal window. Meaning, high speed UPLC
QqQMS/TOFMS types of hybrid LC-MS instrumentation enables
researchers to rapidly acquire qualitative accurate mass precursor and product ion information while simultaneously obtaining quantitative
profiles for most of the detectable components in a single sample at
the same time with the same instrument. This will become especially
important and advantageous to researchers wishing to data-mine
samples that were previously analyzed. For example, quality assurance
managers looking to find underlying trends in failed specimens
samples, high throughput operations with large numbers of samples
being assayed but data review is not conducted in real-time, or any
other situation where the correct analyte or species to monitor was
not evident before injection. Overall, this emerging trend in LC-MS
instrumentation may just be the next paradigm shift offering multidimensional,
temporally resolved, information in a single LC-MS
instrument.
Conflict of Interest
The views expressed in this manuscript are those of the author(s) and do
not reflect the official policy or position of the Department of Army, Department of
Defense, or the U.S. Government.
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