Harnessing Eco-Friendly Solvents for Greener Liquid Chromatography

by | Jun 5, 2024

From water-based mobile phases to bio-derived solvents, sustainable options are on the rise for analytical chemists.

Toxic solvents and wasteful practices no longer define liquid chromatography. The shift towards reverse-phase chromatography has led analysts to replace traditional mobile phase solvents, such as dichloromethane (prohibited by the EPA in 2024), with safer alternatives including ethanol, ethyl acetate, and water. A wave of green innovation is transforming LC, exemplified by three recent studies promoting sustainable practices.

HPLC With Glycerol Mobile Phase 

Derived from renewable sources, glycerol is a non-toxic and biodegradable solvent ideal for green chemistry. A study in Microchemical Journal examined its use as a green mobile phase modifier for reversed-phase liquid chromatography. Researchers tested glycerol-water mixtures on various antiviral drugs, demonstrating that these mobile phases maintained chromatographic performance while significantly reducing environmental impact.

However, controlling the viscosity of glycerol presents a fundamental challenge to its use as a green solvent. As noted in a ChromForum post, glycerol's high viscosity can affect the performance of HPLC pumps, leading to non-linear flow rates and pressure issues. Effective management of a glycerol pump involves control over parameters, such as heat to reduce viscosity, and using wider diameter tubes and valves to ensure reliable chromatographic results.

Green Methods for Pharmaceutical Analysis

A 2024 study published in Scientific Reports developed green methods for pharmaceutical analysis, offering a practical example of low-impact mobile phases. The paper introduces spectrophotometric and HPLC methods for quantifying metoclopramide, a drug widely used to treat nausea.

The spectrophotometric method measures absorbance at 273 nm using ultrapure water as the solvent. The HPLC method uses a mobile phase of ethanol and formic acid with an Extend C18 column and isocratic elution, maintaining a constant mobile phase composition at 1.0 mL/min throughout the run. Both methods are rapid, cost-effective, and environmentally friendly, providing reliable results without matrix interference. These green chemistry techniques highlight the potential for sustainable quality control practices.

Achieving Pure Water Mobile Phases

Developing chromatographic methods that use pure water as the mobile phase, without requiring organic solvents, is a long-standing goal for green liquid chromatography. A recent review by Dembek and Bocian compiled the latest efforts and advancements toward this objective. 

Using pure water as the mobile phase in liquid chromatography can be achieved through two main approaches: elevated temperatures or specialized stationary phases. At higher temperatures, the solvent properties of water are enhanced, allowing it to effectively separate non-polar compounds without the need for organic modifiers. However, this approach requires careful consideration of the thermal stability of both the stationary phase and the analytes of interest.

Alternatively, various stationary phases, including polar-endcapped and polar-embedded phases, can be tailored to work efficiently with pure water. These phases offer high elution strength without organic solvents. The review examines the challenges and benefits of different stationary phase materials and their compatibility with green LC methods, highlighting their potential to reduce toxic waste and improve sustainability in LC applications.


The shift towards green analytical chemistry is a critical evolution for a sustainable future. Advancing green liquid chromatography (LC) requires thoughtful method optimization to handle challenging parameters such as high-temperature columns and engineered stationary phases. With growing regulatory pressure and societal demands for eco-friendly practices, the chromatography community is poised to innovate through continued knowledge sharing.

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