GC/GC–MS

LCGC: What trends do you see emerging in GC or GC–MS?

Phillip James: Increasing levels of regulation across many sectors has resulted in growing numbers of samples requiring analysis, and this has led to several trends in gas chromatography (GC). A shortage of skilled chromatographers means that there is a greater need for instruments that are simpler to operate and maintain, sample preparation also needs to be simplified and automated, and more sophisticated software for interpreting results is needed. There is also a demand for faster analysis times because of this greater number of samples.

I also believe we will see a trend towards greener chromatography. This increased level of testing means a much larger CO2 footprint for the analytical testing industry. I think a move towards greatly reducing the CO2 footprint for each sample is going to become more relevant.

Lorne Fell: An emerging trend is certainly nontarget analysis: the ability to truly discover what is holistically in a sample has been recognized in recent articles, conferences, and workshops. The need for nontarget analyses will continue to branch beyond the typical markets of metabolomics and food, flavour, fragrance into petroleum, food safety (foodomics), and environmental exposure (exposomics).

Another newly developing trend is dual detection for GC and multidimensional GC (GC×GC), particularly the combination of mass spectrometry (MS) with flame ionization detection (FID). These technologies allow researchers to quantify without the use of internal standards for each analyte using a FID because of its near universal response; as well as confirm their identity with MS deconvolution and library searching.

Ulrich Meier: Instruments that are more versatile and easier to use and service with smaller environmental footprints and using less bench space are emerging. Instruments with a more compact design, easy exchangeable injection, and detection techniques are another trend.
Laura McGregor: In recent years, we have seen GC×GC becoming a more routine technique. Until now, users have often shied away from the technology, convinced that it was too expensive, or too difficult, to implement in their laboratories. However, more affordable hardware and simpler workflows mean it is now starting to be adopted by high‑throughput laboratories.

Jack Cochran: On the MS hardware side, the trend for improvements in selectivity and sensitivity continues. There seems to be a move in some application areas from highly selective tandem MS (MS/MS) systems towards accurate mass instruments that can provide selectivity and universal detection simultaneously.

Some chemists argue that further MS sensitivity improvements are not necessary but there are select ultratrace applications, such as determination of brominated dioxins in environmental samples, that do demand better sensitivity. Given the popularity of “just enough” sample preparation methods like QuEChERS, extra MS sensitivity also supports injecting less dirty sample on the GC instrument to reduce the amount of maintenance required on the inlet and column. That maintenance leads to loss of sample throughput.

I do not want to overlook the development of powerful data analysis software as a trend either, especially for accurate mass MS instruments. Calculation of chemical formula, automated searching of web chemical structure databases, generation of Kendrick mass defect plots, and statistical analysis programs really extend the power of these instruments.

LCGC: What is the future of GC or GC–MS?

Phillip James: One area I believe the future of GC lies is with ultra-fast GC (UFGC). The technology has the potential to answer many of the issues facing analysts today. Greatly reduced power consumption for each sample, faster cycle times, smaller instrument footprints, and greater portability are some of the benefits. Greater adoption of this technique will help drive the development of improved detection systems, which are both faster and more sensitive.

Rapid advances in computing power have allowed for new types of data processing that were previously impossible. This will allow new types of detector and vast improvements in automated interpretation of results and data. I also believe that there is still scope for further advancements of GC column technologies to complement UFGC

Lorne Fell: As I mentioned previously, the technologies that are best suited for the nontarget analysis markets will continue to evolve and become more mainstream. These technologies will include multidimensional chromatographic separations, high‑speed, and high‑resolution mass spectrometers. The future, however, will be dominated by the software’s ability to easily and reliably generate chemical and biochemical information out of mountains of data. I believe GC and GC–MS are having a resurgence in popularity with several significant technological advances and, GC is, once again, achieving prominence at major conferences.

Ulrich Meier: GC is migrating to GC–MS, and GC–MS is migrating to GC–MS/MS. MS systems are increasingly replacing systems with specific detectors, such as the electron capture detector (ECD), the phosphorous nitrogen detector (PND), the flame photometric detector (FPD), or the FID because of tighter regulatory conditions and the acceptance of MS by many GC users. There is also limited range of detectable components by non‑MS detectors. Positive identification is still a main motive and more GC laboratories are investing in MS-based configurations.

Laura McGregor: There is a high demand for faster, fully-automated methods with simple reporting and minimal review. Basically, “push button” systems that answer a particular question. For example, analysts commonly want to know: “What’s the difference between sample A and sample B?” Instrument manufacturers will, of course, be striving to provide instruments that answer such questions, although I doubt we will ever be able to match the omniscient analytical systems in TV forensics shows!

Jack Cochran: The future of GC and GC–MS looks very good because some molecules are just always going to be more efficiently analyzed by gas chromatography. And when I say “efficiently”, I’m not only talking chromatographic separation power, but also ionizability, spectral library availability, quantification accuracy, and the cost of analysis.

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

Phillip James: Whilst not a specific industry or application, the increase in regulatory testing has created a trend that only a small percentage of samples analyzed contain compounds of interest above regulatory levels. The majority of samples are either blank or below levels of interest but are still tying up expensive laboratory resources. From this we have seen a requirement for more intelligent systems for the rapid screening of samples with only the positive sample then passed for re-analysis in further detail.

The cannabis industry is an area for big growth in the need for testing throughout the supply chain. With more and more customers realizing the benefits analytical testing can bring right across this industry, this will only grow as further territories legalize the use and the industry matures.

Lorne Fell: Metabolomics is certainly still on a significant growth curve, but the analysis of cannabis is out-pacing all others right now. It will be very interesting to see how it plays out; regulations, legal matters, and methods are still in flux, but there is a large degree of momentum behind it right now.

Metabolomics is such a broad category that one needs to uncover the areas of higher growth. “Exposomics” is certainly gaining a lot of attention and importance.

Ulrich Meier: Hyphenated systems are gaining more interest. The possibility to get analytical information by, for example, hyphenating thermal gravimetric analysis (TGA), infrared (IR), and GC–MS in a single run using a limited amount of sample make it an attractive proposition for material characterization.

GC×GC is an interesting field in academia or for very specialized users, but it still has to gain more acceptance in routine analysis.

Laura McGregor: GC×GC has been long-established as the technique of choice for the petrochemical industry, but recently we have seen a stronger uptake by the environmental sector. For example, environmental contract laboratories are now replacing time-consuming off-line fractionation steps and multiple analyses with a single solvent extract run by GC×GC with a FID.

In some cases, new legislation is actually driving the need for these advanced analytical techniques, for example, the Canadian Ministry of the Environment has now listed GC×GC as an acceptable analytical technique and published multiple regulatory methods on its use with a micro‑electron capture detector (µECD) for monitoring chlorinated species, such as polychlorinated biphenyls (PCBs) and chloroparaffins.

Jack Cochran: Probably life sciences, which seems a bit counter-intuitive given that I often think of big molecules and liquid chromatography (LC) when I think of life sciences. But metabolomics, which involves the determination of small molecule metabolites in a biological system, has exploded over the last few years. Metabolomics research areas include disease diagnosis, fruit flavour improvements, drug development, and environmental impact, just to name a few.

Interestingly, the use of GC–MS for metabolomics overcomes an obstacle for the analysis of polar molecules, by using derivatization to make the compounds GC-amenable. It is worth the extra sample preparation trouble to use GC–MS because LC–MS can suffer from inaccurate quantification in complex metabolomic samples as a result of charge competition effects in electrospray ionization.

LCGC: What obstacles stand in the way of GC or GC–MS development?

Phillip James: I don’t see any real barriers to GC or GC–MS technology development. The advances in computing and production methods mean it is now possible for new concepts to be introduced. There is scope for some truly innovative and disruptive GC technology to appear in the next decade.

Lorne Fell: Obstacles are interesting to discuss because GC and GC–MS have been in the forefront of analytical capabilities for so long. Certainly spectral expansion of existing libraries (NIST etc.) is still necessary because many chemicals are still being discovered and need to be more quickly entered into libraries and published for all to use. For GC specifically, column developments for higher temperature (beyond 400 °C) analytical phases for petroleum applications would fulfil an unmet need in today’s marketplace.

Furthermore, clarity and speed for analytical method approval from governmental regulatory bodies would be highly beneficial.

Lastly, the impression (or myth) that GC and GC–MS is old technology and no longer useful is certainly an obstacle for development and continued adoption- and is certainly not true!

Ulrich Meier: Running multiple instruments in the laboratory with specific software is a limiting factor. GC and GC–MS running on different software platforms require a higher level of training for the user. Solutions integrating all available sample introduction techniques, GC, GC–MS, and MS/MS on a single software platform with easy data exchangeability that also fits for a regulated environment is, in my opinion, still more a wish than a reality.

Laura McGregor: Instrument hardware is constantly evolving, but it seems that the software aspects struggle to keep up with the huge volumes of data that may now be generated from these advanced techniques, especially when using high‑resolution mass spectrometers. This so-called “big data” and the associated need to streamline processing workflows is one of the main obstacles to routine adoption of advanced GC–MS techniques.

For GC×GC, “omics”-type workflows are a key challenge. These require trends and differences to be spotted across huge sample batches, each containing hundreds, if not thousands, of variables. Currently, there is no fast and foolproof solution to this.

Jack Cochran: A major obstacle is the GC system itself, in the context of the analytes and the samples. Only relatively volatile analytes can be determined with GC and GC–MS. Highly polar or high‑molecular-weight compounds can only be chromatographed with difficulty, if at all. Samples containing nonvolatile matrix components can take the GC system down quickly. If you cannot get the compound through the GC, the power of the detector does not matter.

Another obstacle is the inability of GC–MS to distinguish isomers from each other, especially when they coelute on a GC column. This is important because one isomer may be toxic, or contribute most to a flavour or fragrance, versus another isomer. Stationary phase selectivity research seems mostly to be a thing of the past, and this would be a good obstacle to overcome.

A relatively new GC detection system based on vacuum ultraviolet (VUV)spectroscopy offers a potential solution to the isomer determination obstacle because absorbance spectra are based on a molecule’s specific shape. This results in a unique fingerprint for a compound that allows for its spectral deconvolution from coeluting peaks even when they are isomers.

LCGC: What was the biggest accomplishment or news in 2017/2018 for GC or GC–MS?

Phillip James: The growing acceptance of UFGC is the most interesting development. Whilst the technique has been around for many years, the increasing number of companies offering UFGC systems or accessories means it is now being taken seriously. The availability of systems that combine UFGC with conventional air blow chromatography will help drive adoption of the technique by allowing users to move to UFGC methods with the safety net of still being able to fall back on existing methods if required. Further adoption of this technique has the potential to act as a catalyst for other future developments.

Lorne Fell: The most innovative accomplishment that I witnessed this year was the development and description of comprehensive three-dimensional (3D) GC by Robert E. Synovec from the University of Washington.

Ulrich Meier: Hyphenation of instruments such as TGA–IR–GC–MS, GC–inductively coupled plasma (ICP)–MS, or high performance liquid chromatography (HPLC)–ICP–MS. These techniques are becoming available in a wider market.

Laura McGregor: As far as GC×GC is concerned, the biggest change over the past couple of years is the significant expansion of the application range, driven partly by more flexible instrument configurations. For example, GC×GC has now been applied to challenges as diverse as identification of cancer biomarkers, characterization of paper, monitoring human decomposition odour, and profiling illicit drugs. Looking forward, we are expecting this trend to continue, with advances in sample introduction, parallel detection incorporating novel detectors, soft ionization, and development of new stationary phases all helping to provide more information than ever before on the composition of complex samples.

Jack Cochran: For me it’s seeing applications of what I consider two exciting new approaches to GC detection: atmospheric pressure chemical ionization (APCI)-MS and VUV spectroscopy. APCI‑MS can offer 10 times (or more) sensitivity improvement for some analytes compared with electron ionization MS. This type of mass spectrometry’s soft ionization promotes molecular ion formation, which is very important for compound identification. The environmental community is embracing this new technology for analysis of halogenated persistent organic pollutants-just one example of its utility.

VUV spectroscopy offers a unique selectivity compared with any other detectors currently in the GC space. Strong applications include analysis of gasoline‑range samples, and determination of terpenes in flavours and fragrances and cannabis. Both applications benefit from absorbance spectra deconvolution to simplify complex samples.

Phillip James is the Managing Director of Ellutia.

Lorne Fell is a Separation Science Product Manager at Leco Corporation.

Ulrich Meier is a Business Line Leader Chromatography at PerkinElmer LAS GmbH.

Laura McGregor is a Product Marketing Manager at SepSolve Analytical.

Jack Cochran is the Senior Director of Applications at VUV Analytics.