Integrative Analysis of Pharmacokinetic and Metabolomic Profiles for Predicting Metabolic Phenotype and Drug Exposure Caused by Sotorasib in Rats.

ABSTRACT: Sotorasib is a novel targeted inhibitor of Kirsten rat sarcoma (KRAS) (G12C) that has shown exciting tumor-suppressing effects not only for single targeted agents but also for combination with immune checkpoint inhibitors. However, no integrative analysis of the pharmacokinetics (PK) and pharmacometabolomics (PM) of sotorasib has been reported to date. In the present study, a sensitive and robust high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was firstly developed and fully validated for the quantitation of sotorasib in rat plasma. After one-step protein precipitation, sotorasib and an internal standard (carbamazepine) were separated on a Waters XBrige C₁₈ column (50 mm × 2.1 mm, 3.5 μm) and analyzed in electrospray ionization positive ion (E

SUBMITTER: Du P 

PROVIDER: S-EPMC9017425 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature