The present study describes the development of a novel analytical approach that can reduce the consumption of organic solvents in the charge transfer (CT)-based spectrophotometric analysis by 50-fold. The proposed approach employed 96-microwell assay plates for carrying out the reaction. In this approach, the CT reaction between electron-donating analyte and electron-accepting reagent was performed in microwells (200-µL of organic solvent) and the color signals were measured by microwell-plate reader. The optimum conditions for the proposed approach were established for two antihypertensive drugs namely ramipril (RML) and lisinopril (LSL) as model compounds for the electron-donating analytes, and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as a -electron acceptor. Under the optimum conditions, Beer’s law was obeyed in the concentration ranges of 6 – 100 and 6 – 60 g mL1 for RML and LSL, respectively. The limits of detection were 0.97 and 1.1 g mL1 for RML and LSL, respectively. The precisions of the methods were satisfactory; the values of relative standard deviations did not exceed 1.1%. The proposed approach was successfully applied to the analysis of pharmaceutical dosage forms that contain the investigated drugs with good accuracy and precision. The results of the proposed approach were compared favorably with those of the reported methods. The approach described herein is of great practical value in pharmaceutical analysis because it offers the reduction in the exposures of the analysts to the toxic effects of organic solvents, reduction in the analysis cost by 50-fold, and it has a high throughput property. Although the approach was validated for RML and LSL, the same methodology could be used for electron-donating analyte for which a CT reaction can be performed.