Molnupiravir detection by tandem mass spectrometry

Abstract

Background: After the COVID-19 epidemic that broke out in 2019, studies on antiviral drugs accelerated. In clinical studies with both re-purposed drugs and newly discovered drugs, the need for reliable methods that allow the measurement of drug levels in the blood has increased. Molnupiravir is one of the drugs considered under the treatment of COVID-19 and is on the agenda with conflicting findings. However, there are limited validated methods that report the measurement of molnupiravir levels. Therefore, our aim in this study was to develop a practical, robust validated tandem mass spectrometric method that allows the measurement of molnupiravir levels. Methods: Method development studies for the measurement of molnupiravir levels were performed with a liquid chromatography-tandem mass spectrometry (LC-MS / MS) device and the method was validated according to CLSI (The Clinical & Laboratory Standards Institute) protocols. Linearity, recovery, precision, stability, matrix effect, carry-over and lower limit determination studies were performed. Results: The method was linear with a correlation coefficient value of 0.993 in the range of 20 ng/mL-20 µg/mL. The sensitivity of the method was 20 ng/mL. The CV% obtained from the intra- and inter-assay studies was below 6.2% and the mean recovery was over 95%. Total analysis time was 5 minutes for each sample. Conclusions: A simple, cost-effective, reliable tandem mass spectrometric method with high sensitivity and accuracy based on protein precipitation alone has been developed for the measurement of molnupiravir levels.