Identification, characterization, and in silico ADMET prediction of nirmatrelvir and its degradation products using HPLC‐PDA and LC‐QTOF‐MS/MS

Nirmatrelvir and its five DPs were efficiently separated using reverse phase-HPLC. These five DPs were identified and characterized using LC-electrospray ionization (ESI)-Q-TOF-coupled mass spectrometry analysis in the ESI-positive ionization mode. The formation mechanisms of the DPs and the most probable mass fragmentation pathways for both nirmatrelvir and its DPs were elucidated. The developed method demonstrated selectivity, accuracy, linearity, and reproducibility, making it appropriate for quality control of nirmatrelvir and future research studies. Additionally, the physicochemical and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of nirmatrelvir and its DPs were predicted using ADMET predictor software. The toxicity profile revealed that DP2 and DP3 have teratogenic effects while DP1 and DP3 caused phospholipidosis.