Mobile phases in RP-HPLC are often composed of an aqueous part and an organic solvent. The selection of the organic solvent is a key step in the development of a green analytical method. With the objective to take into account operator safety and decrease environmental impact, the comprehensive assessment of green solvents by Capello et al. [28] showed ethanol to be among the best green solvent candidates. Its low toxicity and its sourcing from renew-able sources reduce risks by minimizing the environmental impact and health hazards. Indeed, this organic solvent is usable in liquid chromatography and has a cost compatible with a routine use in a control quality service [29]. However, the use of ethanol as organic solvent can represent a risk if poor UV chromophore compounds are analyzed and its high viscosity can generate high pressures, especially in the case of stationary phases with particle size under 2 m[1,29]. These limitations were overcome by the use of compounds with chromophores and UHPLC. Unfortunately, the use of ethanol led to lower peak efficiencies than acetonitrile even if columns with particle size under 2 m were used [30]. Moreover, an increase of the flow rate had a higher impact on peak efficiency which decreased faster with mobile phases containing ethanol compared to acetonitrile [30]. Consequently, peak efficiency would be considered herein as a critical parameter since small amounts of analytes must be quantified.