A cornerstone in transferring a classical liquid chromatography (LC) ultraviolet/visible (UV/Vis) method into greener and sustainable analytical method should consider the safety and toxicology of the used organic solvent in the method. Organic solvent portions used in the mobile phase may be replaced by a green solvent that is ideally bio-based and biodegradable to increase the greenness of the method. However, the implementation of a new solvent for high performance liquid chromatography (HPLC-UV/Vis) requires consideration of its environmental and health impact, cost-effectiveness, user-friendliness, and impact on the analytical performance and suitability of its chromatographic method. Existing greenness, blueness, and redness metrics expressing whiteness for evaluating the comprehensive sustainability of methods after solvent replacement overlook the chromatographic suitability of the selected solvent, this may potentially lead to suboptimal solvent replacement and an incomplete view of its capabilities. In this work, the authors present a Universal Suitability and Sustainability Index (USSI), a sixteen-parameter scoring system that quantifies four main factors for complete evaluation of a new solvent for implementation in HPLC. This index is beyond the white analytical chemistry principle. The four main factors are chromatographic suitability, greenness, blueness, and redness. Three of these factors, are based on available tools and metrics to evaluate the environmental and practicability impact on the health, and the analytical performance of the method. The fourth factor is added as an important criterion to judge the suitability of the solvent for HPLC analysis and to give an overview about its analytical applicability. The new index has been used to evaluate traditional liquid chromatographic as well as green solvents-based methods to give a universal overview that aids users to drive a rapid impression on the weakness and strength aspects and makes it easier to judge the selection of the solvent and the evaluation of the overall method sustainability.