The increasing environmental concerns and regulatory restrictions on toxic conventional solvents have driven the search for sustainable alternatives. Dimethyl isosorbide (DMI), a bio-renewable solvent, has shown potential as a replacement for short-chain glycol ethers, although its use as solvent in liquid chromatography (LC) is underexplored. This study presents a physicochemical characterization of DMI with a particular focus on its application as an innovative solvent in LC analyses. The partition coefficient (log P = −0.44) was determined using the OECD 107 method, and viscosity measurements for DMI and its mixtures with water and ethanol were conducted at 25 °C, 40 °C, and 60 °C. Viscosity ranged from 1.28 mPa·s at 60 °C to 2.62 mPa·s at 40 °C. The Central Composite Face 2³ experimental design for studying the chromatographic behavior of DMI confirmed that 50% (v/v) DMI can be effectively utilized in the mobile phases, at a column temperature of 40 °C, with backpressures ranging from 160 to 300 bar and a UV cut-off at 240 nm. Its effectiveness as an eluent in LC was demonstrated for the quantification of methylparaben and propylparaben in pharmaceutical formulations. This study highlights DMI’s promise as a sustainable bio-renewable alternative to conventional organic solvents used as eluents in LC, supporting eco-friendly practices in pharmaceutical analysis.

Two hydrophilic interaction liquid chromatography (HILIC) methods for simultaneous determination of the major alkaloids (morphine, codeine, thebaine, oripavine, papaverine and noscapine) in opium poppy straw (Papaver somniferum L., Papaveraceae) were developed.The chromatographic behavior of target alkaloids was investigated on two different HILIC stationary phases: bare silica (Si-HILIC) and zwitterionic (ZIC-HILIC). Systematic optimization of the methods was carried out by use of chemometrics. A full factorial design of the experiments was utilized for assessment of the influence of acetonitrile share, ionic strength and the pH value of the mobile phase buffer on several chromatographic responses. The central composite circumscribed design of experiments was used for the robustness testing during the method validation.The separation of the alkaloids was obtained within close retention window on both columns with optimized gradient elution. The ZIC-HILIC method had advantage over Si-HILIC method in terms of sensitivity, robustness and cost. This method was found suitable for determination of the morphinane alkaloids from poppy straw.