Molnupiravir Bioanalytical Method Development and Validation in Rat Plasma by LC-MS/MS Detection and Application to a Pharmacokinetic

This work aims to propose a novel method for detecting the concentration of molnupiravir in rat plasma that has been developed and verified. This approach makes use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology. Furthermore, the method’s pharmacokinetic applicability in rats was assessed. Phenyl, 250 x 4.6 mm, 5 μm analytical column, operating at room temperature, was utilized to accomplish separation. The investigation employed a mobile phase consisting of a 40:60 v/v combination of 0.1% tri fluoro acetic acid and methanol at a 1.0 mL/min flow rate and an injection volume of 10 μL. The liquid chromatography (LC) procedure was carried out for four minutes. In +ESI mode, the mass spectrometer was in operation. The determination of the mass-to-charge ratio transitions for molnupiravir and D7-Molnupiravir (m/z 330.34→82.46 and 337.46→286.11, respectively) was accomplished through the utilization of multiple reaction monitoring (MRM. The concentration ranges for molnupiravir were determined to be 6.25 to 50.00 ng/mL, with a correlation coefficient 0.9996. The precision and accuracy of HQC, MQC, LQC, and LLQC were found to be 98.34, 98.83, 98.13, and 97.85%, respectively. In pharmacokinetic studies, it was observed that molnupiravir exhibited an average AUC0-t value of 65 ng-hr/mL and a Cmax value of 43.120 ng/mL in rats. In conclusion, the validated created approach has effectively demonstrated the determination of pharmacokinetic parameters subsequent to the oral administration of molnupiravir in wistar rats.