The hydrophilic interaction UPLC-MS/MS method was used for the quantification of saracatinib in HLMs. Small changes to the N-methyl piperazine in drug design might improve the metabolic stability of new derivatives compared with that of saracatinib.
Evaluations using the DEREK software and analyses of in silico WhichP450 results suggest that minor modifications or substitutions within the phthalazin-1-one (52%) and piperazine moieties (24%) account for 76% of olaparib in drug development.
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.
According to evaluations performed using the DEREK and WhichP450 modules, slight changes or substitutions in the piperazine ring during drug development could yield new derivatives with improved safety and metabolic stability compared to EST.
Veliparib exhibited a relatively slow extraction ratio, with a low Clint of 22.23 mL min−1 kg−1 and a long t1/2 of 36.48 min. Minor replacements within the pyrrolidine ring (96%) in veliparib may increase the metabolic stability and safety profile.