Dimethyl carbonate as a green solvent in ternary solvent systems for liquid chromatography: Investigation of miscibility limits and mobile phase viscosities.

The extensive use of organic solvents in high-performance liquid chromatography (HPLC) contributes to a considerable environmental impact, driving the search for more sustainable solvents. In this context, dimethyl carbonate (DMC) has recently emerged as a promising, greener organic modifier due to its low viscosity and high elution strength. However, its limited miscibility with water requires the use of a ternary solvent. As comprehensive physicochemical data on such systems remain limited, the present study investigates the miscibility and viscosity behaviour of ternary mobile phase systems composed of DMC, water, and one of four common LC co-solvents (acetonitrile, methanol, ethanol, and isopropanol). Miscibility measurements were performed across the entire ternary space to establish the minimum co-solvent fractions required to maintain miscibility across a 0-100% organic mobile phase gradient. When using acetonitrile, significantly higher co-solvent fractions are needed (75% v/v) as compared to the case where alcohols are used (required fractions around 50% v/v). Subsequently, dynamic viscosity measurements were conducted, showing that DMC generally reduces the viscosity of traditional LC solvent mixtures, except when added to acetonitrile/water. Accordingly, calculated kinetic gain factors were below 1 for acetonitrile/water mixtures containing DMC relative to the binary mixture without DMC. This indicates that, while the addition of DMC increases the greenness of acetonitrile/water mixtures, it also slightly decreases efficiency. In contrast, the addition of DMC to the alcohol-based solvent systems resulted in potential gains of up to 1.6 in analysis speed and 1.3 in efficiency compared to binary co-solvent/water systems. For these systems, DMC therefore enhances chromatographic performance.