Nirmatrelviris anantiviral drug that acts asa 3C-likeprotease inhibitor. It is used with the combination of Ritonavir for the treatment of COVID-19. The World Health Organization strongly recommended this medicine to moderate and mild COVID patients, which is now the best option for COVID-19 therapeutics against SARS-CoV-2. As a result, there is an urgent need for quick and low-level quantitative analytical techniques for Nirmatrelvir and its products by focusing on the mass-compatible buffer with a shorter run time as the target. Accordingly, we developed a procedure with the following optimized conditions; mobile phase: 0.10 % formic acid in water and acetonitrile (55:45 %v/v), column oven temperature: 45 °C, flow rate: 1.0 mL/min with 15 min run time in isocratic elution mode. The developed procedure is linear and accurate from 0.20 to 500 µg/mL. Forced degradation studies in all solid and liquid degradations were executed to demonstrate the method's stability indicative capacity. To demonstrate the peak purity of the desired compound orthogonally, all degradation samples were then subjected to peak purity analysis using an HPLC PDA (High-performance liquid chromatography photodiode array) detector and LCMS (Liquid chromatography-mass spectrometry) analysis. The literature methods were developed with highly concentrated buffers which cause ion suppression in LCMS and increase backpressure in HPLC systems but the proposed method is conducive and more sensitive (limit of quantitation: 0.20 µg/mL and limitation of detection: 0.0 6 µg/mL) than the reported methods and has a wide linearity range as well. The developed technique has been fully validated by ICH (International Council for Harmonisation) guidelines. Further, it has been evaluated for greenness character using the AGREE (Analytical GREEnness) statistical tool and the obtained score is 0.61 out of 1.