Key Points
• Ferguson highlights the move toward replacing traditional acids like trifluoroacetic acid (TFA) and difluoroacetic acid (DFA) with methanesulfonic acid (MSA) in peptide analysis. This change reduces environmental impact due to lower toxicity and better biodegradability. However, it comes with trade-offs, including potential impacts on chromatographic performance and sensitivity, requiring careful method optimization.
• A key strategy for sustainability is reducing mobile phase volumes, which directly reduces solvent waste and resource consumption. This is especially relevant for high-throughput labs. However, Ferguson notes practical limitations, such as ensuring method robustness and reproducibility at lower flow rates, which can affect data quality if not well-controlled.
• Ferguson emphasizes the environmental benefits of on/off LC–MS mechanisms compared to traditional continuous-flow systems. On/off systems reduce solvent and energy usage when not actively analyzing samples. Nonetheless, they require method redesign and equipment adaptation, especially in older systems not originally built for intermittent use.
As the pharmaceutical industry moves toward more sustainable and responsible practices, the spotlight is turning to analytical techniques—and how they must evolve to meet both scientific and environmental demands. In this special HPLC 2025 interview with LCGC International, we sit down with Paul Ferguson, a leading voice in sustainability in the pharmaceutical sector, to explore the intersection of green chemistry and emerging therapeutics.
Ferguson shares insights on how method design is adapting to support sustainability in the development of new modality therapeutics. We discuss the practicalities and trade-offs of greener alternatives—such as replacing trifluoroacetic acid (TFA) with methanesulfonic acid.
From mobile phase volume reduction to the environmental implications of liquid chromatography–mass spectrometry (LC–MS) flow strategies, this discussion offers a forward-looking perspective on what it means to build analytical methods that are not only effective but also sustainable.
Ferguson addressed the following questions:
• As sustainability becomes a key consideration in pharmaceutical development, how is chromatographic method design evolving to support greener practices, particularly for new modality therapeutics such as peptides and oligonucleotides?
• What are the primary sustainability benefits and trade-offs of using MSA (methanesulfonic acid) as a replacement for TFA/DFA in peptide analysis?
• How can reducing mobile phase volumes serve as a practical strategy for reducing the environmental impact of chromatographic methods, and what limitations might be encountered?
• What impact does the on/off mechanism have on sustainability, particularly in non-optimized LC–MS systems, and how does it compare to traditional continuous-flow approaches?
• Do you have general advice on how separation science can become more sustainable?
Paul Ferguson was appointed professor by special appointment at the Faculty of Science of the University of Amsterdam, Netherlands, in March 2025. His chair, “Separation of Biomacromolecules, with an Emphasis on Sustainable Analytical Science,” is part of the Van ‘t Hoff Institute for Molecular Sciences (HIMS) and endowed by the Bèta Plus foundation. He is also an active member of The Chromatographic Society (ChromSoc) and LCGC international’s editorial advisory board (EAB).