GC–MS

The workhorse technique of GC–MS continues to lead the way in application areas from environmental analysis to food and beverage research.

Joining us for this discussion are Monty Benefiel of Agilent Technologies, Inc.; Julie Kowalski of Restek Corporation; Richard M. LeLacheur and Rohan Thakur of Taylor Technology; Jim Edwards of Thermo Fisher Scientific; and William Goodman and Massimo Santoro of PerkinElmer, Inc.

What new developments in GC–MS have you seen so far this year?

Benefiel: Three decades of continuous technology evolution have made GC–MS one ofthe most common, routine, and easy to implement hyphenated techniques in chromatography. Recent advances in chromatographic and spectrometric selectivity, instrument transportability, and application-ready solutions are continuing to extend the productivity and performance of mainstay GC–MS instruments. For example, new developments in separation technologies such as GC capillary flow devices, MS-MS analyzers, and deconvolution software have led to dramatic increases in GC–MS selectivity — making identification and quantification of trace level compounds in complex matrices reliable and accurate. Developments in low thermal mass GC for rapid heating and cooling of capillary columns have led to smaller instrument form factors and reduced power consumption — making transportable instruments capable of producing laboratory quality data a reality. Finally, GC–MS instruments that are factory configured, pretested, and installed as application specific solutions are helping to make laboratory systems operational and productive faster than ever.

Kowalski:I feel that the success of LC–MS-MS in combination with recent GC–MS-MSproduct launches has moved this technique from something interesting totalk about to the lab bench. Analysts understand the benefits of tandemmass spectrometry and have become much more comfortable with thetechnique. This has lowered the apprehension threshold for people to tryGC–MS-MS. I am seeing a growing number of GC–MS-MS users through mydirect interactions via technical service, conferences, andcollaborations. With the more predictable ionization process for GC–MSversus LC–MS, will we see some analyses, especially quantitative work,shift from LC–MS-MS to GC–MS-MS?

LeLacheur and Thakur:The renewed focus on negative ion CI from the various vendors on their GC triple quadrupole mass spectrometer platforms is a new development. This is a key GC–MS-MS application area that can yield significant improvements in specificity and sensitivity compared to LC–MS-MS.

Edwards:The focus for GC–MS appears to be continuing to involve increased performance attributes (i.e., sensitivity, precision, and linear dynamic range) that are maintainable over long periods of time (i.e., robustness and reliability). Users want to know that they have access to the full capabilities of their systems, regardless of what may have been analyzed in the days or weeks before. This focus on improved hardware attributes is necessarily connected to improved software capabilities, as developing hardware that can run more samples per unit time means there is more data that has to be processed, reviewed, and reported per unit time. Additionally, as GC–MS as a technology is more widely used by a variety of users with a variety of experience and educational backgrounds, bringing these hardware and software capabilities to those users in an easy-to-use, intuitive manner is also a strong focus.

Goodman and Santoro:Thus far in 2010 the developments in bench-top, single-quadrupole GC–MS have been evolutionary. The products in the market are constantly being tweaked and the designs and manufacture streamlined. This results in systems that are more sensitive, faster, reliable, and easier to use.

Which industries currently benefit the most from the use of GC–MS?

Benefiel:GC–MS is widely used in the environmental, food safety, forensics,sports doping, and toxicological fields where low-level detection incomplex matrices is critical. In general, any industry dealing with theanalysis of complex GC samples today will benefit most from the newadvances in instrument selectivity discussed above.

Kowalski:Segments of the environmental industry rely heavily on GC–MS. Environmental testing can necessitate trace level analysis and confidentcompound identification to meet EPA and legal requirements. GC–MS isideally matched to achieve to these needs. For example, volatilesanalyses, like EPA Method 524, are ideally suited for gas chromatographybecause of these compounds have high volatility, which is needed forsuccessful GC analysis. The combination of retention time matching withmass spectra matching adds confidence compound identification withoutthe need for dual column analysis.

LeLacheur and Thakur:All industries involved in small molecule analysis, especially below m/z 400, can benefit from GC–MS. Some applications, such as food and environmental, can benefit from straightforward GC–MS analysis when the targeted analytes are directly amenable to GC separation. Pharmaceutical and biomarker applications often utilize derivatizations that, when combined with negative CI, can produce order-of-magnitude improvements in assay quantitation limits. The analyses of steroids in biological fluids at physiologically relevant levels are a good example of the power of GC–MS-MS in the field of clinical diagnostics and oncology research.

Edwards:GC–MS continues to be widely used in environmental and food safety laboratories, and continues to have a strong place in forensics, toxicology, and clinical analyses. In addition to these areas, GC–MS is often used in research and academic laboratories, and as the areas of energy and biofuels continue to grow, GC–MS has a place there as well.

Goodman and Santoro:Single-quadrupole GC–MS is becoming a commodity for many applications in various market segments. We are seeing strong focus in the safety and quality aspects of food and consumer-product testing. These industries are using GC–MS to monitor processes and products that have not been monitored before. The development of new methods is accelerated and improved as a result of knowledge and history of GC–MS analysis in other areas such as environmental and forensics. Existing methods have been modified and adapted to new matrices.

This knowledge and history has reduced the time needed to design and validate new analytical approaches. The number of analysts with GC–MS experience and method-development capabilities has further improved the creation of food and consumer-product test methods.

What is the GC–MS application area that you see growing the fastest?

Benefiel:Although currently small compared to the application areas discussedpreviously, metabolomics is probably seeing the greatest rate of growth.Food safety and environmental applications are much larger and continueto show signs of robust growth. In a much more general sense, any GC–MS application dealing with complex analysis will grow fast as newdevelopments in instrumentation (e.g., MS-MS analyzers) and dataanalysis software extend productivity and performance.

Kowalski:Homeland security benefits from the advent of portable field gaschromatographs, mass spectrometers, and GC–MS instruments, as well asmobile lab units outfitted with GC–MS instrumentation. Civilian uses foremergency responders can determine the safety of the location quickly, aswell as start to collect data that may become important in a forensicsinvestigation. Applications include detection of chemical warfareagents like toxins and explosives, volatile and semivolatile compounds,and toxic industrial compounds. It is critical to military personneland emergency responders that these types of compounds can be detectedon-site, quickly, and with the confirmation provided by massspectrometry.

LeLacheur and Thakur:While environmental chemistry, sports medicine, and forensic applications will continue to grow, fields such as "lipidomics" and steroid analysis in pharmaceutical R&D could see a potential increase. Any application where LC–MS fails to deliver either in terms of selectivity or sensitivity is ripe for GC–MS, provided the technique can be supported both in terms of sample preparation and advances in instrumentation. Often GC–MS is the right tool for the job, however, the simplicity of LC–MS sample preparation influences the outcome in favor or simplicity.

Edwards:The global nature of our food supply chain places a premium on rapid and accurate analyses of imports and exports; as such, the food safety area may be one are that is growing very quickly. Increased emphasis on global warming and energy may also be a burgeoning market.

Goodman and Santoro:GC–MS is growing in most application areas; the general trend that we continue to see is movement from traditional GC detectors, such as FID and ECD, to MS. Two drivers behind this trend are confirmation and productivity.

The spectral confirmation data from an MS is very valuable, eliminating the need for additional GC runs and reducing the time necessary to make decisions based upon analytical data. Additionally, we are seeing customers further utilizing the fast-heating and cooling capabilities of the GC technology with MS detection. MS in many cases reduces the requirement for complete resolution of analytes and matrix, enabling faster chromatographic runs. This again is a result of the continuing need for increased productivity — our customers need to get more work done with the current workforce.

How do you expect GC–MS to change in the future? What obstacles do you think stand in the way?

Benefiel:Advances in chromatographic and spectrometric selectivity will be asimportant as enhanced sensitivity. Sensitivity improvements alone willnot be the answer if the compounds of interest cannot be separated fromsample interferences. This is the reason why technologies such ascapillary flow devices, MS-MS analyzers, and deconvolution software arekey developments that are enhancing the application of GC-MS today. The need for bringing laboratory quality GC-MS measurements closer to where the sample is taken will drive continued developments in transportable instrumentation. Instrument form factor, power consumption, and ease of operation are obvious areas of needed development, but matching the proven data quality of gold standard laboratory GC-MS will be the key challenge.

Kowalski:As the need for trace level analysis in very complex matrices increases,GCxGC mass spectrometry could come to the rescue. Comprehensivetwo-dimensional GC increases peak capacity by applying two independentseparations involving a serial column configuration with differentstationary phases.

Chromatography is performed on the first column, and then effluent fromthe first column is continually and quickly focused and injected by amodulator onto the second column. We recently employed this techniqueto determine pesticide residues in dietary supplements. Dietarysupplement extracts can be so complex as to make trace-level pesticidedeterminations problematic, if not impossible, by common chromatographicmethods. The obstacle here is similar with any uncommon technology,people become concerned that a seemingly complex analytical technique isdifficult to use and will not be as rugged as familiar techniques.

LeLacheur and Thakur:Design and execution of sample preparation remains arduous for negative CI GC–MS applications, which limits the potential use of this powerful tool. Innovation in this general area, i.e., making sample preparation inclusive of derivatization chemistry easier, would significantly help the resurgence of GC–MS in areas outside environmental chemistry and forensics. The other obstacle remains the limited instrument market size, which influences GC–MS instrument development and innovation. For example, a GC-based high-resolution mass spectrometer with accurate mass capability stable across several weeks could see a lot of utility in many application areas.

Edwards:There will be a continued emphasis on improving analytical attributes, such as sensitivity, linearity, and robustness, while also improving overall workflow through software automation and sophisticated data review systems (where the GC–MS chemist often spends a majority of their time). There may be an increased desire for smaller and/or portable units, for flexibility in both stationary and mobile laboratory design. One challenge to designing transportable or smaller scale systems is balancing the needs of the systems in terms of ruggedness, size, and analytical capabilities — what level of performance is expected or needed in a field-based unit versus what the same characteristics for a stationary lab unit are; and is there a market for a smaller stationary system that may have differing performance characteristics.

Goodman and Santoro:GC–MS will continue to become faster, more sensitive, and easier to use. The workforce in analytical facilities will continue to be lean — this will create a situation where more needs to be done with less hands. One obstacle that will affect GC–MS is the efficiency and reliability of the sample preparation. As the laboratory workflow continues to be evaluated, people will look past the instrumentation and towards the sample preparation.

We know that the instrumentation available today is very efficient, while the sample preparation workflow has largely been overlooked. In many cases, this is where the bottlenecks and quality issues arise. Our expectation is that there will be increased focus on the processes, which feed samples into the GC–MS laboratories. Automation will provide increased productivity as well as improved reproducibility.

Technologies such as thermal desorption and headspace will be re-evaluated and expanded as a result of the ease-of-use and reliability. Other approaches like heartcutting and backflushing will be used to more efficiently solve matrix and co-elution problems.

If you are interested in participating in any upcoming Technology Forums please contact Associate Editor Meg Evans for more information. Next month’s forums will focus on the HPLC/Chiral and Pharmaceutical Analysis markets.