Development and Validation of a New RP-HPLC Method for the Simultaneous Estimation of Nirmatrelvir, Ritonavir and Molnupiravir in Formulated Nanosponges, Plasma Samples and its Pharmacokinetic Study

Background:

Nirmatrelvir and Ritonavir are used in combination (Paxlovid®) in order to treat COVID-19. Thus, the goal of the current study was to create an easy-to-use, accurate, and sensitive method for the preparation of nanosponges utilising High-Performance Liquid Chromatography (HPLC) to simultaneously estimate Nirmatrelvir and Ritonavir in plasma samples and prepared nanosponges.

Materials and Methods:

Nanosponges containing Nirmatrelvir and Ritonavir were prepared using ethyl-cellulose. Formulated Nanosponges are useful to increase the safety and efficacy of Nirmatrelvir and Ritonavir combinational therapy and also support Therapeutic Drug Monitoring (TDM). Patients are presently advised not to use Paxlovid® because of the challenging TDM but who are most likely to become really ill from COVID-19 infections should benefit from these nanosponges.

Results:

The proposed method’s validation was conducted in accordance with ICH recommendations Q2R1, demonstrating its good linearity and accuracy, and precision. We saw from the selectivity studies that the retention durations of the medications under investigation did not exhibit any additional peaks. 89.63% w/w and 89.98% w/w, respectively, were computed as the entrapment efficiency of nanosponges for Nirmatrelvir and Ritonavir, using the established method to determine their entrapment efficiency in formed nanosponges. With correlation coefficient (R2) values of 0.998 and 0.996, respectively, the observed concentration in plasma linearity for Ritonavir was 2842 ng/mL to 24550 ng/mL and for Nirmatrelvir was 2791 ng/ mL to 25414 ng/mL.

Conclusion:

The new approach showed that both medications were stable over the course of the trial and the three freeze-thaw cycles.