Stability indicating RP-HPLC technique for simultaneous estimation of nirmatrelvir and ritonavir in their new copackaged dosage form for COVID-19 treatment

Abstract

Abstract RP-HPLC technique was developed and optimized for simultaneous identification and estimation of nirmatrelvir (NIR) and ritonavir (RIT) in their new copackaged tablet. Stability of nirmatrelvir (NIR) was studied after exposure to different five stress conditions; alkali, acid, heat, photo and oxidation degradation. The chromatographic separation was achieved using VDSpher PUR 100 ODS (4.6-mm x 15-mm), 3.5 μm column and mixture of 0.03 M potassium di-hydrogen phosphate buffer pH 4 and acetonitrile (45:55, v/v) as mobile phase. The column temperature was set at 40 °C, flow rate at 1mL/min and UV detection at 215 nm. The NIR and RIT retention times were 3.94 ± 0.08 min and 9.08 ± 0.1 min, respectively. Linear relationship was established in range of (1.5–105 µg/mL) for NIR and (1–70 µg/mL) for RIT with good reproducibility. The found mean percentage recoveries of nirmatrelvir (NIR) and ritonavir (RIT) were 100.03% and 99.85%, respectively. The developed method shows very good sensitivity as the LOQ and LOD were found to be 3.001 & 0.990 µg/mL, respectively for NIR and 2.765 & 0.912 µg/mL, respectively for RIT. The developed approach was validated concerning to ICH guidelines and applied successfully for the simultaneous estimation of NIR and RIT in their new copackaged dosage from. The results of assay using the proposed approach were compared statistically to the results found by applying the published one with good agreement.

Keywords

• Nirmatrelvir (NIR)
• Ritonavir (RIT)
• RP-HPLC
• Stability indicating
• Copackaged tablet