Quantification of KRAS inhibitor sotorasib in mouse plasma and tissue homogenates using liquid chromatography-tandem mass spectrometry

Sotorasib is a KRAS inhibitor with promising anticancer activity in phase I clinical studies. This compound currently under further evaluation as monotherapy and combination therapy against solid tumors. In this study, liquid chromatography-tandem mass spectrometric method to quantify sotorasib mouse plasma eight tissue-related matrices (brain, liver, spleen, kidney, small intestine, intestine content, lung, testis homogenates) was developed validated. Protein precipitation using acetonitrile utilized 96-well format extract erlotinib (internal standard) from tissue homogenates. Separation of the analytes performed on an Acquity UPLC® BEH C18 column by gradient elution methanol 0.1% formic acid water at flow rate 0.6 ml/min. detected triple quadrupole spectrometer positive electrospray ionization selected reaction monitoring mode. A linear calibration range 2–2,000 ng/ml achieved during validation. Accuracy values were 90.7–111.4%, precision (intra- interday) between 1.7% 9.2% for all tested levels investigated matrices. The successfully applied investigate pharmacokinetics accumulation female wild-type mice.