Micro-flow HPLC, that is, liquid chromatography performed with small I.D. chromatography columns, typically 0.3 mm, and low flow rates (4 ul/min), provides a significant savings in solvent usage and mixed waste generation over conventional HPLC. Wide-scale use of micro-flow HPLC would reduce toxic waste generated by chemical researchers in academia and industry by millions of liters per year. By using a 0.3 mm I.D. column on a micro-flow HPLC and reducing the flow rate to 4.3 ul/min so that the linear velocity of the mobile phase through the column is equivalent to a conventional HPLC, a mobile phase volume savings of greater than 99% is realized. Any HPLC method that has been validated and developed over the past decades can be directly transferred to micro-flow HPLC by scaling only column I.D., flow rate, and sample volume, yielding the same separation, sensitivity and retention times, but with a significant savings in solvent usage and mixed waste generation.