85
therefore requires a skilled operator and is associated with significant cost and
downtime. In practice, problems related to LC performance and failures, combined
with issues associated with the interface between the LC and MS, are more common
than problems related to the MS system itself.
There are also significance challenges associated with the development of a practical analytical method. It can be a major challenge to efficiently extract the
analyte(s) of interest from what is frequently a complex sample matrix containing
hundreds or more abundant components. There are always losses of the target
analyte(s) and to varying degrees matrix components remain in the sample extract
depending on the nature of the sample and the workup steps adopted. Selecting and
optimizing an extraction method – especially for multi-component analysis of low
abundance components – is therefore a (very) complex endeavor. A key factor in
minimizing instrument downtime and producing acceptable results is the introduction of “clean” samples into the LC-MS (or GC-MS) system. For all these reasons,
developing a practical, cost-effective, robust, automated and validated analytical
method for a specific application can be a very time-consuming and costly task.
The widespread adoption of LC-MS (/MS) methods has been fueled by the need
for high-quality data suitable for addressing a diverse array of applications and most
commonly, the LC-MS/MS work is performed on a triple quadrupole mass spectrometer operated in the selected reaction monitoring (SRM) mode. The primary
strength of this instrument configuration is its ability to separate sample components, detect, identify and quantify them – all in a single run. Examples applications
include the analysis of agricultural chemical residues, carcinogens, toxins (e.g.,
mycotoxins), veterinary drugs, additives, other environmental contaminants or
endogenous components in food samples. In addition, these systems are used to
measure biomarkers of disease or dysfunction in human urine, blood or tissue
samples.
5.2 Direct Analysis MS Approaches as an Alternative to GC/
LC Combined with Tandem Mass Spectrometry
GC-MS/MS and LC-MS/MS have worked very well to separate the components of
a complex (solution phase) sample, ionize them, and sequentially transfer the resulting ions into the vacuum system of the mass spectrometry for identification and/or
quantification. As discussed above, however, the cost of the equipment, the long,
complex and expensive sample preparation time, the analysis time itself (constrained by the chromatography step), the complexity of instrument operation, the
time for test development, and the overall cost of test delivery mean that GC- or
LC-MS/MS cannot be adopted routinely for many applications, despite their power.
There is now, however, a very long list of direct, open air surface sampling/ionization approaches available (sometimes called ambient ionization methods), and
these can serve as alternatives. This list includes extractive electrospray ionization
5 Direct Mass Spectrometry as a Practical Analytical Strategy for High Speed, High…
therefore requires a skilled operator and is associated with significant cost and
downtime. In practice, problems related to LC performance and failures, combined
with issues associated with the interface between the LC and MS, are more common
than problems related to the MS system itself.
There are also significance challenges associated with the development of a practical analytical method. It can be a major challenge to efficiently extract the
analyte(s) of interest from what is frequently a complex sample matrix containing
hundreds or more abundant components. There are always losses of the target
analyte(s) and to varying degrees matrix components remain in the sample extract
depending on the nature of the sample and the workup steps adopted. Selecting and
optimizing an extraction method – especially for multi-component analysis of low
abundance components – is therefore a (very) complex endeavor. A key factor in
minimizing instrument downtime and producing acceptable results is the introduction of “clean” samples into the LC-MS (or GC-MS) system. For all these reasons,
developing a practical, cost-effective, robust, automated and validated analytical
method for a specific application can be a very time-consuming and costly task.
The widespread adoption of LC-MS (/MS) methods has been fueled by the need
for high-quality data suitable for addressing a diverse array of applications and most
commonly, the LC-MS/MS work is performed on a triple quadrupole mass spectrometer operated in the selected reaction monitoring (SRM) mode. The primary
strength of this instrument configuration is its ability to separate sample components, detect, identify and quantify them – all in a single run. Examples applications
include the analysis of agricultural chemical residues, carcinogens, toxins (e.g.,
mycotoxins), veterinary drugs, additives, other environmental contaminants or
endogenous components in food samples. In addition, these systems are used to
measure biomarkers of disease or dysfunction in human urine, blood or tissue
samples.
5.2 Direct Analysis MS Approaches as an Alternative to GC/
LC Combined with Tandem Mass Spectrometry
GC-MS/MS and LC-MS/MS have worked very well to separate the components of
a complex (solution phase) sample, ionize them, and sequentially transfer the resulting ions into the vacuum system of the mass spectrometry for identification and/or
quantification. As discussed above, however, the cost of the equipment, the long,
complex and expensive sample preparation time, the analysis time itself (constrained by the chromatography step), the complexity of instrument operation, the
time for test development, and the overall cost of test delivery mean that GC- or
LC-MS/MS cannot be adopted routinely for many applications, despite their power.
There is now, however, a very long list of direct, open air surface sampling/ionization approaches available (sometimes called ambient ionization methods), and
these can serve as alternatives. This list includes extractive electrospray ionization
5 Direct Mass Spectrometry as a Practical Analytical Strategy for High Speed, High…