Greening pharmaceutical applications of liquid chromatography through using propylene carbonate–ethanol mixtures instead of acetonitrile as organic modifier in the mobile phases

Substitution of acetonitrile (ACN) as organic modifier in mobile phases for liquid chromatography by mixtures of propylene carbonate (PC) and ethanol (EtOH) may be considered a greener approach for pharmaceutical applications. Such a replacement is achievable without any major compromise in terms of elution order, chromatographic retention, efficiency and peak symmetry. This has been equally demonstrated for reverse phase (RP), ion pair formation (IP) and hydrophilic interaction liquid chromatography (HILIC) separation modes. The impact on the sensitivity induced by the replacement between these organic solvents is discussed for UV–vis and mass spectrometric detection. A comparison between Van Deemter plots obtained under elution conditions based on ACN and PC/EtOH is presented. The alternative elution modes were also compared in terms of thermodynamic parameters, such as standard enthalpy (ΔH0) and entropic contributions to the partition between the mobile and the stationary phases, for some model compounds. Van’t Hoff plots demonstrated that differences between the thermodynamic parameters are minor when shifting from ACN/water to PC/EtOH/water elution on an octadecyl chemically modified silicagel stationary phase. As long as large volume injection (LVI) of diluents non-miscible with the mobile phase is a recently developed topic having a high potential of greening the sample preparation procedures through elimination of the solvent evaporation stage, this feature was also assessed in the case of ACN replacement by PC/EtOH.

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► Acetonitrile was successfully replaced by propylene carbonate/ethanol mixtures in LC mobile phases.
► RPLC, IPLC and HILIC applications are presented; sensitivity concerns related to UV–vis and MS detection are discussed.
► Van Deemter plots obtained under ACN and PC/EtOH elution modes are compared.
► Comparison of thermodynamic parameters for the elution alternatives was achieved.
► Injection of immiscible diluents was studied under the two elution approaches.