Insight: Helium supply and the increase in the use of hydrogen as a gas chromatography carrier gas.

Why hydrogen is a serious contender as a gas chromatography carrier.

Helium is the second-most abundant element after hydrogen, created in stars by the process of nuclear fusion of hydrogen. In contrast, terrestrial helium is rare and is formed through the underground radioactive decay of uranium (²³⁸U). Over time, this helium migrates through permeable rock formations and is released into the atmosphere, where it is quickly lost into space.

Where the rock is impermeable, helium is trapped alongside methane natural gas deposits. Cryogenic high-pressure fractional distillation is used to extract the helium and nitrogen from the less volatile methane. This crude helium contains 50% to 70% helium and 1% to 3% residual methane, with the remainder mainly of nitrogen with a small amount of hydrogen. It is cooled to about -200°C and the resultant liquid methane and nitrogen are drained off. A small amount of air is added and the oxygen combines with the remaining hydrogen impurity by catalytic conversion to produce water vapour. The resultant gas is again cooled and the water is drained off.

Final trace impurities are then removed by pressure swing adsorption – a technique used to separate some gas species from a mixture of gases, typically air, under pressure – which renders ultra-high-purity analytical-grade helium.

Unfortunately, the decay of uranium has a half-life of 4.5 billion years, and therefore the geological formation of helium is negligible compared with the volume of human extraction. Helium is therefore considered to be non-renewable.

Helium crisis?

Are we on the cusp of a helium crisis? There are many examples of scientists predicting that global helium reserves will be depleted in 20 to 35 years but we don’t believe this is credible. The Mineral Commodities Summaries 2023, produced by the US Geological Survey, part of the US Department of the Interior, reports that global reserves of helium total 39,850,700 million cubic metres. The Geological Survey has very detailed accounts of reserves and production, but it does not give consumption figures. If we assume consumption is equivalent to the production of 160,000 million cubic metres, then reserves for 249 years are calculated (4). Based on 2019 data (1), supplies are adequate for an estimated 335 years,

The largest terrestrial helium reserves are in the US. In 2022, the US was responsible for 46.9% of global production (4). About 75% of this helium is extracted from natural gas of the Panhandle-Hugoton field, which straddles Texas, Oklahoma and Kansas. This natural gas is helium-rich, with an average concentration of 0.586% (2). Helium has been found in concentrations as high as 8% in some global sources of natural gas. In the US, the lowest practical helium concentration that can economically justify extraction is about 0.3% (3). Qatar is the second-largest producer, with 37.5% of global production in 2022. The US and Qatar together accounted for 84.4% of world production in 2022, followed by Algeria (5.6%), Russia (3.1%) and Australia (2.5%) (4). 

According to many sources, we are still being affected by a helium shortage that began in 2019 as a result of the prolonged closure of the world’s largest purification facility in the US and critical maintenance at another two of the world’s eighth-largest purification plants. This became more pronounced in 2021 and 2022. The price of helium saw an increase of 300% between 2000 and 2020.

Changes to hardware required

Much helpful literature is available from instrument manufacturers about the changes to hardware and chromatographic conditions required when substituting helium with hydrogen as carrier gas. The manufacturer’s example chromatograms using hydrogen show complex sample components being beautifully resolved in less time than it takes to change a GC injection septa. This is great. In terms of the time taken for any particular GC analysis, hydrogen always produces the best results, but there are other considerations too.

The only unavoidable problem with the use of hydrogen is that it may react with some sample components during chromatography. This would be a significant worry if the aim of the analysis was the identification of unknown sample components. The concern with the flammability of hydrogen has largely been addressed by instrument manufacturers offering oven-leak sensors and gas-flow controllers that will shut off the gas flow if unexpected increases in flow due to back-pressure drops are noted.

Butterworth, like other laboratories, has decided to commission hydrogen generators, which will remove the safety risks associated with handling large gas cylinders, along with the cost and environmental impact of transporting them over long distances.

With Gas Chromatography – Mass Spectrometry (GCMS), there may be a requirement to use a modified ion source for best operation with hydrogen, and these are becoming available. When changing from helium to hydrogen, it is a relatively quick operation to change ion sources on modern instruments, and many do not require venting of the system vacuum to do so. The MS spectra obtained using hydrogen rather than helium may exhibit different ion fragment intensities from those of our current spectral libraries, which were produced using helium.

It is hoped that spectral libraries obtained using hydrogen will soon be available.. Specific detectors such as Electron Capture may not operate as effectively while using the required flow rate of hydrogen required for packed-column or mega-bore capillary analysis.

Regulatory compliance

When budding chromatographers ask me when the move to hydrogen will happen, my usual reply is “when the pharmacopeia says so”. The type of carrier gas is not an allowable adjustment in any of the pharmacopeia, and I believe the prescription of hydrogen in new and revised monographs will have more of an impact on the use of hydrogen than the price and supply of helium in the short term.

At present, and for the foreseeable future, helium, nitrogen and hydrogen will all be required as carrier gases, based on compliance requirements. There has been movement in the pharmacopeia; for example, in the revised USP Monograph for Castor Oil (2019), the determination of fatty acids has been changed from a titration to a GC assay using hydrogen as a carrier.

Indeed, there are now a number of methods in both the PhEur and USP requiring hydrogen, and so it looks like we are seeing the predicted shift starting to come into play. I think that for methods using nitrogen, there may be little sense in costly revalidation using hydrogen. A measure of the speed of historical updates to compendial methods can be seen in the number of monographs still requiring the use of packed columns and nitrogen carrier gas.  

One point often misunderstood is that while hydrogen is a major step forward in terms of productivity, in terms of chromatographic efficiency (theoretical plates), nitrogen is surprisingly the best. For any given column, the carrier gas with the highest molecular weight will generate more theoretical plates because diffusion is minimised. Nitrogen gives about 15% more plates than hydrogen, the trade-off being that in order to achieve this, the run time would have to be 3.5 times that of hydrogen. The optimum nitrogen flow rate being 12cm/s, compared with 40cm/s for hydrogen, according to van Deemter curves.

Looking to the future

As protocols for the development and validation of chromatographic procedures for non-compendial APIs and raw materials are being agreed by the projects department, Butterworth is advising clients of the benefits of hydrogen, after taking into account concerns such as hydrogenation of sample components. In closing, and perhaps not least, the financial savings realised from a move from helium cylinders to hydrogen produced by in-situ generators is very significant and will have a real impact on analytical costs.  

Link to Associated Whitepaper

References

1. LCGC blog, 11/4/22. https://www.chromatographyonline.com/view/not-another-helium-crisis-
2. Brown, A (2019). Origin of Helium and Nitrogen in the Panhandle-Hugoton Field of Texas, Oklahoma and Kansas, US. AAPG Bull. 103 (2), 369–403. doi:10.1306/07111817343
3. National Academies of Sciences, Engineering and Medicine (2000). The Impact of Selling the Federal Helium Reserve. Washington, DC: The National Academies Press. https://doi.org/10.17226/9860
4. Mineral Commodities Summaries 2023, US Geological Survey, US Department of the Interior.           https://pubs.usgs.gov/periodicals/mcs2023/mcs2023.pdf