Helium, the second most abundant element in the universe after hydrogen, is produced in stars through nuclear fusion. However, on Earth, helium is relatively scarce. It is primarily generated by the underground radioactive decay of uranium (238 U). Over time, this helium migrates through porous rock formations and eventually escapes into the atmosphere, where it dissipates into space. Due to its physical properties, helium is the only substance that escapes the atmosphere and is lost in space. Because of its inertness, if this were not the case, the concentration of helium in the atmosphere, which is stable at about 5.2 ppm, would constantly rise as the formation of geological helium continued.
When helium encounters impermeable rock, it becomes trapped alongside natural gas deposits, predominantly methane. A process known as cryogenic high-pressure fractional distillation is employed to extract helium and nitrogen from these less volatile methane deposits. The resulting crude helium mixture typically contains 50% to 70% helium and 1% to 3% residual methane, with the remainder being mostly nitrogen and a small amount of hydrogen. The mixture is then cooled to approximately -200°C, allowing the liquid methane and nitrogen to be drained off. A small amount of air is added, facilitating the catalytic conversion of any remaining hydrogen into water vapor, which is removed through further cooling and drainage.
To achieve ultra-high-purity helium, final trace impurities are removed through a method called pressure swing adsorption. This technique, commonly used to separate specific gases from a mixture under pressure, ensures the production of analytical-grade helium. However, the production of helium through the radioactive decay of uranium is an incredibly slow process, with a half-life of 4.5 billion years. This means that the natural formation of helium is negligible compared to the rate at which humans extract it, rendering helium effectively non-renewable.
Are We Facing a Helium Crisis?
Concerns about a potential helium crisis have been raised, with some scientists predicting that global reserves could be depleted within 20 to 35 years. However, these claims are not universally accepted. According to the US Geological Survey's Mineral Commodities Summaries 2023, global helium reserves amount to approximately 39,850,700 million cubic meters. While the Geological Survey provides detailed accounts of helium reserves and production, it does not specify consumption rates. Assuming consumption matches the production of 160,000 million cubic meters, helium reserves could last for 249 years. Based on data from 2019, this could extend to 335 years.
The largest proven terrestrial helium reserves are located in the United States, which accounted for 46.9% of global production in 2022. Approximately 75% of this helium is extracted from the Panhandle-Hugoton natural gas field, spanning Texas, Oklahoma, and Kansas. This field contains helium-rich natural gas, with an average concentration of 0.586%. In some US and other global sources, helium concentrations as high as 8% have been recorded. The minimum economically viable concentration for helium extraction in the US is around 0.3%. Qatar is the second-largest helium producer, contributing 37.5% of global production in 2022. Together, the US and Qatar produced 84.4% of the world's helium that year, followed by Algeria (5.6%), Russia (3.1%), and Australia (2.5%).
Despite this, a helium shortage that began in 2019 due to the prolonged closure of the world's largest purification facility in the US and maintenance issues at two other major plants continues to impact supply. This shortage became more pronounced in 2021 and 2022, leading to a 300% increase in helium prices between 2000 and 2020.
Adapting to Hardware Changes
Instrument manufacturers have provided extensive guidance on the hardware and chromatographic adjustments needed when substituting helium with hydrogen as a carrier gas. For instance, hydrogen often results in faster and more efficient separation of complex sample components in gas chromatography (GC). While hydrogen can significantly reduce analysis time, it also has some drawbacks.
One key concern is the potential for hydrogen to react with certain sample components during chromatography, which could complicate the identification of unknown substances. The flammability of hydrogen has also been a concern, but modern instruments are equipped with safety features such as oven-leak sensors and gas-flow controllers that automatically shut off the gas flow if unexpected changes are detected.
Like many other laboratories, Butterworth has opted to use hydrogen generators. These generators eliminate the safety risks associated with handling large gas cylinders and reduce the environmental impact of transporting them over long distances.
In Gas Chromatography-Mass Spectrometry (GCMS), using hydrogen may require a modified ion source for optimal performance. These modifications are increasingly available, and changing ion sources on modern instruments is a relatively quick process that often doesn't require venting the system vacuum. However, it’s important to note that mass spectra obtained using hydrogen may differ from those in existing spectral libraries, which were generated with helium.
Spectral libraries using hydrogen are anticipated to become more widely available. However, certain detectors, such as Electron Capture Detectors, may not function as effectively at the hydrogen flow rates required for packed-column or mega-bore capillary analysis.
For further technical insights on transitioning from helium to hydrogen, refer to our detailed whitepaper here.
Regulatory Considerations
When asked about the transition to hydrogen, my usual response is, "When the pharmacopoeia says so." Currently, the type of carrier gas is not an adjustable parameter in any pharmacopoeia. I believe the adoption of hydrogen in new and revised monographs will have a greater impact on its use than helium's price and supply issues in the short term. For now and for the foreseeable future, helium, nitrogen, and hydrogen will all continue to be required as carrier gases to meet regulatory compliance. However, there has been some movement in the pharmacopoeia. For example, the revised USP Monograph for Castor Oil (2019) now specifies the use of GC with hydrogen as the carrier gas for determining fatty acids.
An increasing number of methods in both the European and US Pharmacopoeias also require hydrogen, indicating a gradual shift. However, due to the associated costs, there may be little incentive for methods currently using nitrogen to revalidate them using hydrogen. The pace of historical updates to compendial methods can be seen in the continued use of packed columns and nitrogen carrier gas in some monographs.
One often overlooked point is that while hydrogen offers significant productivity gains, nitrogen is surprisingly the most efficient carrier gas in terms of chromatographic efficiency (theoretical plates). The carrier gas with the highest molecular weight generates more theoretical plates for any given column due to reduced diffusion. Nitrogen produces about 15% more plates than hydrogen, though achieving this requires a run time 3.5 times longer than hydrogen. The optimal flow rate for nitrogen is 12 cm/s compared to 40 cm/s for hydrogen, as van Deemter curves indicate.
Looking Ahead
As protocols for developing and validating chromatographic procedures for non-compendial APIs and raw materials are being established, Butterworth advises clients on hydrogen benefits while also considering concerns such as the potential hydrogenation of sample components. In conclusion, the financial savings from switching from helium cylinders to in-situ hydrogen generators are significant and will notably impact analytical costs, as well as reduce the carbon footprint associated with the production of steel cylinders and transportation to and from the supplier to the laboratory.
Closing Thought
Yes, we must reduce helium usage because it is finite. However, due to climate concerns, we must reduce our usage of natural gas, and the economic consequence and technical difficulty of returning natural gas to geological storage after extracting helium and doing this without loss would be considerable.
