A fixed dose combination of Darunavir and Ritonavir is effective for the treatment of human immunodeficiency virus (HIV) infection. For the simultaneous es t imation of the fixed dose combination, two chemometrics methods are developed based on ratio mean centring (RMC method) and the difference between the adjacent data points (DBADP method). The methods employ spectral ratio manipulation, wherein the ratio s p ectral data is subjected to mean centring in the RMC method, and the difference between the adjacent data points in the ratio spectra are used for the DBADP method. For the data processing, a simple software program written with Python and MATPLOTLIB was u sed. Beer’s law was valid in the range of 10 60 µg/ml for Darunavir and 2.5 15 µg/ml for Ritonavir in both methods. The assay results obtained for the marketed formulation were found to be 99.78% and 99.36% for Darunavir and Ritonavir, respectively, by th e RMC method: Assay results were 99.91% and 100.76% for Darunavir and Ritonavir respectively by DBADP method.