Sotorasib (AMG 510) is a first-in-class KRAS inhibitor that received accelerated US FDA approval in 2021 for the treatment of patients with -mutated locally advanced or metastatic non-small-cell lung cancer. : An LC-MS/MS method was developed and validated for the determination of sotorasib in human plasma to support clinical development studies. Samples were prepared using protein precipitation and analyzed by LC-MS/MS using gradient elution with a calibration standard curve range of 10.0-10,000 ng/ml. Stable isotope labeled C, D -sotorasib was used as an internal standard. The method fully met FDA guidelines for all validation parameters, including precision, accuracy, selectivity, matrix effect, recovery and stability and has been extensively used to support multiple clinical studies.