Fifty Years of Ion Chromatography: An Interview with Brett Paull

Looking back over 50 years, what do you consider the most transformative milestone in the development of ion chromatography (IC)—and why?
The quality of the chromatography itself is always of utmost importance, and so the constant enhancements in separation efficiency made through multiple column and stationary phase innovations over the years would get my vote. These include the constant improvements in agglomerated ion-exchange phases (1), the emergence and improvement of grafted phases (2-3), the more recent decrease in particle sizes from 10 μm to 4 μm (“fast” columns), and, of course, the development of hydroxide-selective phases to complement the emergence of the eluent generator. In terms of efficiency, these stationary phase developments have seen ion chromatographic separations move much closer to those of reversed-phase liquid chromatography (RPLC) separations than we could have otherwise imagined.

How has IC evolved to meet the demands of increasingly complex sample types compared to other LC techniques?
I believe IC has evolved substantially to allow practitioners to apply the modern technique to increasingly complex samples. The development of eluent generation technology allows the user to program complex gradients with precision, and the improvements in separation efficiency allow the separation of an increasing number of ions using these gradient programs. A large range of available column variants and selectivity adds to this capability, meaning that the desired separation can usually be found for even the most challenging samples

What were the key technological innovations that elevated IC from a niche technique to a mainstream analytical tool?
If we park suppressors to one side, for me, the most innovative development was electrolytic eluent generation, both for anions and for cations. “Just add water” ion chromatography was ahead of its time as a green technology and is still such a great advantage in rapid method development when using IC to analyze a new or unknown sample. Second to this, I would say suppressed IC coupled to mass spectrometry (MS) is enabling so many new and exciting applications, and I would imagine we will see a great many more IC–MS instruments in routine ion analysis laboratories in the coming years as this combination becomes more mainstream (4).

In what areashas IC had the most lasting and unique impact compared to other LC modalities?
IC is a big technique in environmental analysis, particularly for nutrient anions, where it’s the gold standard method. However, its application across the food and beverage industries is also very significant if you consider the importance of sugars and organic acids. The use of IC in pharmaceutical analysis is also very important, and when analyzing for inorganic ions, there still isn’t really any other viable routine alternative.

As someone deeply experienced in IC, what common misconceptions do you hear from reversed-phase LC users, and how would you correct them?
We still get reviewers for paper submissions stating that ion chromatography cannot be coupled with MS due to the high concentrations of salt within the eluents used. These reviewers seem to be about 40 years out of date in their understanding of suppressed ion chromatography. Clearly, eluent suppression—from which we get our eluted anions or cations in a background of pure water—is compatible with MS, and no high salt levels are in sight!

Can you share a case where IC outperformed other LC techniques in a surprising or critical application?
We have an ongoing program on the use of IC and, in particular, IC-MS in the analysis of Antarctic ice-cores for new and previously unreported ionic climate change proxies. Ice core samples are limited in volume and obviously very precious (given the cost of obtaining them), and so today we are using capillary format IC-MS to help us detect >25 anion species in as little as 180 μL of sample, which no other technique would even come close to. (5,6).

How has the role of IC in regulatory and compliance testing evolved, and what gives it an edge in trace-level ionic analysis?
It is obviously a multi-analyte methodology, as opposed to alternative spectroscopic or electrochemical methods, and is highly sensitive, routinely able to deliver low-ppb detection limits. I also suspect its excellent linearity exceeds that of all other alternative analytical methods for inorganic ions.

What do you see as the future for IC in an era increasingly dominated by mass spectrometry and multidimensional separations?
I see the future embracing MS as a detection option. In fact, we are already doing so. To use MS for inorganic ions is problematic for many applications without a separation step, and so I don’t see MS alone being commonly applied to inorganic and organic anions, without their separation by IC.

If you had to make a case for every LC laboratory to add IC to their toolbox, what would be your strongest argument today, especially in terms of ROI and versatility?
I would argue that method development is quick, and once developed, it is automated, robust, and reliable, requires little or no hazardous chemicals, and produces little waste. The simple answer is that if the laboratory is tasked with ion analysis, what else would they use?

What advice would you give to a young chromatographer considering specializing in IC, and how does the field stay vibrant and innovative going forward?
Innovation in IC is no different from innovation in other modes of LC. Innovation continues in the stationary phase development, column formats, instrument capability, and application to challenging sample types. My advice is, if your research requires or involves ion analysis, become well trained in IC; if it doesn’t…then don’t.

References
1. Stillian, J. R.; Pohl, C. A. New Latex-Bonded Pellicular Anion Exchangers with Multi-Phase Selectivity for High-Performance Chromatographic Separations. J. Chromatogr. A 1990, 499, 249–266.

2. Pohl, C. A.; Saini, C. New Developments in the Preparation of Anion Exchange Media Based on Hyperbranched Condensation Polymers. J. Chromatogr. A 2008, 1213, 37–44.

3. Zatirakha, A. V.; Pohl, C. A. Hybrid Grafted and Hyperbranched Anion Exchangers for Ion Chromatography. J. Chromatogr. A 2023, 1706, 464218.

4. Barron, L.; Paull, B. Simultaneous Determination of Trace Oxyhalides and Haloacetic Acids Using Suppressed Ion Chromatography–Electrospray Mass Spectrometry. Talanta 2006, 69, 621–630.

5.Sanz Rodriguez, E.; Poynter, S.; Curran, M.; Haddad, P. R.; Shellie, R. A.; Nesterenko, P. N.; Paull, B. Capillary Ion Chromatography with On-Column Focusing for Ultra-Trace Analysis of Methanesulfonate and Inorganic Anions in Limited Volume Antarctic Ice Core Samples. J. Chromatogr. A 2015, 1409, 182–188.

6. Sanz Rodriguez, E.; Plummer, C.; Nation, M.; Moy, A.; Curran, M.; Haddad, P. R.; Paull, B. Sub-1 mL Sample Requirement for Simultaneous Determination of 17 Organic and Inorganic Anions and Cations in Antarctic Ice Core Samples by Dual Capillary Ion Chromatography. Anal. Chim. Acta 2019, 1063, 167–177.

Follow the LCGC Interview series this week to celebrate 50 years of ion chromatography with individual interviews with Joachim Weiss, Chris Pohl, and Brett Paul giving their views on the past present, and future of ion chromatography.

Professor Brett Paull (BSc, PhD, DSc) took up his first lectureship at the University of Tasmania from 1995 to 1997, before moving to Dublin City University (DCU), Ireland (1998–2011). In 2011, Brett rejoined the University of Tasmania as a Professor of Analytical Chemistry. From 2014 to 2019 Brett was Director of the Australian Centre for Research on Separation Science (ACROSS), and from 2015-2020 the Director of the ARC Training Centre for Portable Analytical Separation technologies (ASTech). Brett is currently Director of the ARC Training Centre for Hyphenated Analytical Separation Technologies (HyTECH).