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 <i>in silico</i> toxicity
Mohamed W. Attwa, Ali S. Abdelhameed, Haitham AlRabiah, Adnan A. Kadi
Abstract
An UPLC-MS/MS method was established for assessing avapritinib in HLMs matrix. In silico analysis suggests that minor structural changes to the methyl pyrazole moiety in drug design may improve the metabolic stability relative to avapritinib.
Topics & Concepts
MicrosomeMetabolic stabilityChemistryHuman liverMetabolic pathwayToxicityPharmacologyMetabolismMoietyBiochemistryChromatographyHigh-performance liquid chromatographyDrugMetabolic rateGastrointestinal tractReceptorStromal cellDrug metabolismElutionSolventPharmacokineticsChemical stabilityEndocrinologyInternal medicineHuman plasmaBioassayChronic Lymphocytic Leukemia ResearchBiochemical and Molecular ResearchColorectal Cancer Treatments and Studies