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Gas Chromatography

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Whether we know it or not, we rely on a host of analytical techniques in many aspects of our lives, from developing medications to keeping our food safe to enforcing the law. Many of the compounds that need to be assessed, however, are in complex mixtures and therefore chemical separation techniques, including chromatography, are at the heart of many analytical protocols and laboratories.

There are a range of chromatography techniques that exploit different properties of potential analytes and are consequently each suited to different purposes. Broadly, they can be subdivided into gas chromatography (GC) and liquid chromatography (LC). In this article we are going to focus on GC, how it works, its pairing with downstream techniques and what its applications are.

Section quick links

What is gas chromatography and how does it work?
Gas chromatography data handling
Multidimensional gas chromatography
Combining gas chromatography with other analytical techniques
Applications of gas chromatography

-          Petrochemical

-          Biopharma

-          Personal care products

-          Drug discovery

-          Food and beverage

-          Forensics

-          Environmental

-          Metabolomics, lipidomics and proteomics

-          Cannabis science

Working towards a greener future in gas chromatography

What is gas chromatography and how does it work?

Separation of analytes by GC is based on the physical and chemical properties of the compounds within the sample. Samples may be solid, liquid or gas but may require preparation steps prior to introduction to the GC instrument.

For an analyte to be suitable for GC separation, it must be volatile enough to enable it to be carried through the system, but thermally stable to prevent its degradation during the separation process. Consequently, the technique is typically used for organic molecules and gases below 125 kDa.

Samples are introduced into a GC instrument in an inert carrier gas – the mobile phase. This is heated, causing the sample to vaporize. The carrier gas containing the vaporized sample is then passed over the stationary phase and interactions here cause the chemical components within the sample to separate out according to their physical and chemical properties. Different stationary phases can be utilized depending on the analytes of interest.

Interaction of analytes with the GC stationary phase in turn impacts how quickly they elute from the column and this is recorded by the GC detector. Different types of detector can be used depending on the properties of the analytes of interest.

Whilst GC is commonly used for analyzing samples that are easily vaporized, detection of low-level ionic impurities can be challenging. This is often due to contamination from previous injections and careful troubleshooting, which can be time consuming, is required.

For compounds where their polarity or volatility are not amenable to efficient elution from a GC column, pre-treatment steps, known as “derivatization”, may be necessary to achieve detectable analytes.

Gas chromatography data handling

It is of key importance to be able to extract useful information from the sea of data generated from GC analyses. Users must be able to process it in a meaningful way and even identify problems that may require refinements of the methodology, troubleshooting or maintenance of the instrument. Targets for further analyses may also be identified at this point, for example where peaks cannot be resolved.

Storage of large quantities of data is another important consideration, one for which many have turned to cloud solutions to accommodate. Data repositories which can be freely mined by other users are a valuable source for expanding the utility of generated GC data, particularly in a research setting.

Efficiency considerations and data compliance, especially in high throughput settings or those linked to the supply chain, whether in food or pharmaceuticals, are important factors in the systems a company may choose for handling its GC data. Consequently, many commercial laboratories use some form of chromatography data system (CDS) to manage the information. There are many options and suppliers to choose from, so it’s important to select a CDS that’s right for your particular needs and applications. However, even then improper use can result in regulatory breaches.

Increasingly, the solutions offered by vendors of GC instruments are not just concerned with the chemical analyses, but encompass data processing, data handling and service packages. Metrics on instrument performance can be collected that enable streamlining recommendations, servicing and maintenance to be apportioned efficiently and with less hands-on time required.

Multidimensional gas chromatography

For high complexity samples or where trace detection is required, multi-dimensional GC can be utilized, which is particularly useful where there are crowded or co-eluting analyte peaks that hinder effective separation. Here, a fraction of the eluent from the first round of GC is subjected to a second GC separation, normally using a GC column with different properties, permitting effective separation.

Combining gas chromatography with other analytical techniques

Separation techniques like GC can be hyphenated to other detection technologies. GC is most frequently used in combination with mass spectrometry (MS), whereby MS is used in place of the GC detector. It can also be hyphenated to other spectral detection techniques such as Fourier-transform infrared spectroscopy (FTIR). Where complex mixtures are involved, combining GC with one or more other techniques can be powerful in enabling accurate and sensitive identification of target molecules.

Applications of gas chromatography

Separation by GC offers speed, sensitivity and simplicity for detecting and identifying chemical components in even complex mixtures, right down to trace levels. Consequently, these properties make GC a favorable technique in a number of application areas.

 - Petrochemical

The petrochemical industry provides excellent examples of complex analytes such as crude oil, which contains thousands of compounds covering a wide range of molecular weights and boiling points. GC is a key technique at every stage of the process from prospecting, through the refining process, to testing and formulating the final products and ensuring compliance with industry and environmental regulations.

- Biopharma

In the purification of biopharmaceutical products, GC plays an instrumental role. By the nature of the industry, process efficacy and efficiency for large scale purification are key requirements.

- Personal care products

Consumer products that aren’t directly consumed, like fragrances, creams, lotions, toiletries and cosmetics, must still be tested to ensure their safety and the absence of carry-over from the production process.

- Drug discovery

In drug discovery, GC is an important tool for ensuring the purity, safety and quality of drug components and the final drugs that go to market. There is a risk that solvents used during the production process may remain in the product. The chemical, volatile nature of many solvents therefore makes GC a popular choice for their detection. Drug recalls that hit the headlines, such as Zantac, highlight the important role that these analyses play in drug safety. In this case nitrosamine, identified as a likely carcinogen, was the culprit. Nitrosamines have been identified in a number of drugs and are thought to form during drug manufacture or contaminate raw materials or packaging.

- Food and beverage

When it comes to the food industry, there are multiple facets to analytical testing requirements, including a range of safety, quality, and authenticity aspects. On top of this, producers want to improve their products and make them as enjoyable for consumers as possible whilst minimizing costs and streamlining processes. Understanding the chemistry behind our eating and drinking experiences is therefore important for the food and beverage sector’s research and development efforts.

Even a subcategory, such as contaminant detection, encompasses a broad range of substances from mycotoxins to pesticides and can require detection capabilities even at low concentrations. Consequently GC can be a useful tool, offering selectivity and sensitivity for trained users. The ability of GC to separate organic compounds out of complex mixtures, including other substances like lipids, acids, minerals and proteins, also gives it great utility within food and beverage analysis. This has enabled detection of everything from pesticide traces in baby food to insecticides in eggs, to the substance that causes cork taint in wine. Improvements in GC and its hyphenated systems, particularly in relation to food matrix challenges, have reduced downtime and improved system robustness, important for the high throughput seen in many food testing settings.

Dioxins and related chemicals are another GC target that have been attracting increasing attention, as they can persist and accumulate in the environment and pass into the food chain where they can be extremely toxic, even at low levels.

Food analysis requirements don’t stop once the food is packaged either. Food contact contaminants, including transfer from the packaging itself, are an area of concern and one to which GC is applied.

Water, whilst being a much less challenging matrix, can be a hub of contamination and its cleanliness is of paramount importance for the environment and consumers. This necessitates water testing at multiple points in the environment and the drinking water system. Even the disinfection process itself can introduce harmful substances, so effective testing is key.

Whilst in some cases analysts are looking for a specific target or targets in their analyses, the target is not always known. Untargeted screening is particularly important here and also helps to identify emerging contaminants.

Microplastics are increasingly being looked for and identified in foods and beverages, although their impact on our health is still yet to be determined. Thermal analysis paired with GC and MS is one of the tools available for scientists in these continuing investigations.

In the wine industry, GC has been used at many stages of the production process. With increasing problems with wildfires in wine-producing areas, GC has been applied to the detection of taint from wildfire smoke in the fruit, which can impact flavor, prior to wine production. At the other end of the process, GC is also revealing the chemistry behind wine bouquet, giving insights into our sensory experiences.

One drawback with GC in a food and beverage setting is that it does not offer the portable or handheld format of some spectroscopy platforms designed for rapid on-site testing and therefore fulfills a different analytical role.

- Forensics

GC is playing a key role in forensic analyses, both in fraud detection and in the war on illicit drugs.

Food and beverage fraud is a multimillion dollar industry, that not only cons purchasers and undermines the economy, but may put consumers’ health at risk. High value goods, such as vintage wines, spirits, olive oil and manuka honey are prime targets for fraudsters. However, even lower value bulk items that are easily substituted, such as dried herbs and milk powder, have been targeted.

There is an ongoing arms race between law enforcement and those developing and altering illicit designer drugs. As analytical tools become available to detect one group of compounds, others are springing up, some of which are incredibly potent even in small quantities. Therefore, analysts require techniques that are highly specific and sensitive to detect and identify the offending substances. The synthetic opioid family of fentanyls have been a particularly problematic group of substances. From GC spectra, the structures of as yet unknown fentanyls that are not in analytical libraries can be predicted, helping scientists to keep up with emerging dangers.

The matrices in which illicit drugs need to be detected can be complex and challenging too, ranging from blood and urine to hair, oral fluid, breath, and sweat. This is, however, a challenge to which GC is well-suited, due to its ability to cope with substance separation from complex mixtures.

- Environmental

GC is used for the detection of known and unknown substances in the environment, sometimes at very low concentrations. These include pesticides, microplastics, dioxins, nicotine, chemical reaction by-products and even explosives. Substances such as organochlorine pesticides can be highly toxic even at low concentrations. Therefore, the selectivity and sensitivity of GC make it well suited to this application. In other applications, such as microplastic analysis, it may be just one a number of techniques used in the detection process, a combination of which can offer greater detection power.  “Environmental” samples are not limited to the outdoor environment either. Indoor spaces such as laboratories, preparation and manufacturing facilities and cleanrooms must all be monitored to detect and prevent unwanted contamination.

Water is a frequent medium for environmental samples, not least as it often links into the consumer system, but other sample types including soil, plant matter, surface swabs and air are used too.

- Metabolomics, lipidomics and proteomics

When metabolomics was still in its infancy, GC-MS was a key technique that enabled researchers to measure metabolites in human urine and tissue, opening doors in systems biology. Now in the omics age, metabolomics, lipidomics and proteomics are providing invaluable insights into health and disease. Thanks to its resolution, reproducibility and peak capacity, GC is still a key analytical tool in this field. Given the sheer size and diversity of the metabolome, enhanced coverage can also be achieved with the use of 2D-GC.

In metabolomics, GC is helping to unravel mysteries at the molecular level that can lead to more accurate time of death estimates. Other areas where it is making a difference include improving the understanding of toxicity mechanisms from medicinal drugs, cosmetic components and contaminants, nutrigenomics, aiding crop scientists in improving herbicides and pesticides and metabolic genome-wide association studies.

Resources like The Human Metabolome Database are helping to bring data together so that researchers can collectively decode the metabolic pathways in our bodies. This is, however, a big challenge, one with which deep learning is lending a helping hand.

In lipidomics, GC has provided data leading to an improved understanding of areas from stem cell differentiation and insights on fatty acids and cholesterol useful for pharma and biotech, to disease risk predictions and assessing product claims in the cosmetics industry. The critical role that lipids play in many cellular processes means the technique is also important for the emerging area of lipid-based disease biomarker research.

In proteomics, GC is one of the armory of fundamental techniques used by scientists to achieve effective protein separation for downstream analysis.

- Cannabis science

In the growing cannabis industry, many analytical needs mirror those seen in the food and beverage, environmental and pharmaceutical sectors. Consequently, GC is also a key analytical tool in this sector. Requirements range from accurate and sensitive (in the parts-per-billion range) detection of pesticide residues used by growers as in many plant-based crops, to testing of edibles and cannabis-based beverages for contaminants such as residual solvents. Some food matrices, such as lactose and sugar, can prove challenging for cannabis analyses, especially when combined with the diversity of cannabinoids and potential for sample heterogeneity when combined into consumer products. However, modified GC-based methods have been fundamental in improving the transparency of cannabis consumables and have been pivotal in overcoming technical analytical challenges.

Due to their volatile nature, GC has been favored for terpene testing. More recently headspace solid-phase microextraction (HSPM) combined with GC–MS has gained popularity here as it is non-destructive and eliminates interferences from co-extracted matrices.

On the side of regulated cannabis-based pharmaceuticals, the final products must also undergo quality control to ensure safety, purity and correct dosing of active ingredients in cannabis-based pharmaceuticals. Unlike some other chromatography-based methods, GC enables potency testing, terpene profiling, pesticide screening and residual solvents analysis, all of which help to protect the consumer market and make GC a versatile tool in this space.

As the cannabis industry continues to grow, it seems likely that GC will continue to be a key tool for cannabis science.

Working towards a greener future in gas chromatography

Whilst GC is an invaluable technique, it is far from environmentally friendly, requiring significant power input to maintain vacuums, pressures and temperature, and generating harmful waste products from running the equipment and the analyses themselves. However, scientists and engineers are working together to create equipment solutions that reduce the environmental impact.