Assessment of the metabolic stability of avapritinib in human liver microsomes using a fast and green UPLC-MS/MS method: screening for structural alarms associated with metabolic lability and in silico toxicity

Key Points

• Avapritinib showed variable metabolic stability when assessed using human liver microsomes, impacting drug design decisions.
• In silico analysis indicates that modifications to the methyl pyrazole moiety can enhance avapritinib's metabolic stability.
• The UPLC-MS/MS method provides a fast and efficient approach for evaluating drug stability in human liver microsomes.
• These findings highlight the importance of computational methods in identifying structural changes that could improve metabolic profiles.