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The first method was the ratio difference, which was based on the measurement of the difference in absorbance between the two wavelengths (210.6 and 216.4 nm) for Ibuprofen and (236.0 and 248.0 nm) for Paracetamol. The second method was constant center method which depends on using the constant found in the ratio spectra. The third method was the mean centering of ratio spectra which measured the manipulated values at 240 nm and 237 nm for Ibuprofen and Paracetamol, respectively. Beer’s law was obeyed in the concentration range of 2–50 μg/mL for Ibuprofen and 2–20 μg/mL for Paracetamol. The recovery % of the accuracy of both methods ranged from 99.64 to 100.56%. Factors affecting the resolution of the spectra were studied and optimized. The three methods are validated according to ICH guidelines and could be applied for the pharmaceutical preparation.enUniversity of IbuprofenParacetamolRatio DifferenceThree smart spectrophotometric methods for resolution of severely overlapped binary mixture of Ibuprofen and Paracetamol in pharmaceutical dosage formArticlehttps://doi.org/