To treat mild to moderate COVID-19, an investigational drug called nirmatrelvir in combination with ritonavir is being researched for which the potential hazards with this are still unknown. Nirmatrelvir has been approved for immediate use by the US Food and drug intake in conjunction with the drug ritonavir for the treatment of mild to medium COVID-19 in grown ups and individuals of more than 12 years who test positive for the virus and are at a high risk to develop severe COVID-19.To quantify the drugs simultaneously in tablet dosage forms, a novel, sensitive and reproducible reverse phase liquid chromatography method has been developed. Thechromatographic separation was performed using Phenomenex (250×4.6mm,5µ particle size) column. The separation and elution were carried out at an ambient temperature using a mobile phase consisting of 0.1% trifluoro acetic acid &acetonitrile in the ratio of 50:50%v/v. The maximum absorbance by UV spectrophotometer shown at wavelength 258.3nm& 271.4nm for nirmatrelvir and ritonavir. Also, 266nm was selected as detector wavelength by a photodiode array detector for the HPLC chromatrographic method.Beer lambert’s law obeyed in the linear range of 37.5-225µg/mL(R2=0.9998) for nirmatrelvir and 25-150 µg/mL(R2=0.9994) for ritonavir. The method shows method and system precision with % RSD less than 1%.The percentage mean recovery was found to be 99.9-100.2%& 100.0-100.2%. The LOD 1.5 µg/mL &1 µg/mL values indicates the method sensitivity. The proposed stability indicating method was validated for precision,accuracy, specificity, selectivity, robustness and stability studies according to ICH guidelines.

RP-HPLC, Nirmatrelvir, Ritonavir, Trifluoro acetic acid, Stability studies.