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 of losartan potassium (LOS) by 50-fold. The proposed approach employed 96-microwell assay plates for carrying out the reaction. In this approach, the CT reaction between LOS and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as a -electron acceptor was performed in the microwells (200-µl of organic solvent). The color signals of the CT complex were measured at 460 nm by microwell-plate reader. The optimum conditions for the proposed approach were established and the analytical procedures were recommended. The proposed approach offered high sensitivity and precision; the limits of detection and quantitation were 2.47 and 7.49 µg ml-1, respectively. The proposed approach was successfully applied to the analysis of pharmaceutical dosage forms that contain LOS with good accuracy and precision, and the results were compared favorably with a reference method. The approach described herein has great practical value in the routine analysis of LOS in quality control laboratories, as 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 LOS, however, the same methodology could be used for any electron-donating analyte for which a CT reaction can be performed.