Simple and rapid quantification of ribociclib in rat plasma by protein precipitation and LC‐MS/MS: An application to pharmacokinetics of ribociclib nanoparticles in rats

Abstract Ribociclib is a cyclin‐dependent kinase (CDK4/6) inhibitor and is a standard of care for treating metastatic breast cancer. The drug has moderate oral bioavailability and exhibits permeability‐controlled absorption. Novel formulations to enhance ribociclib pharmacokinetics are being developed and tested in rats. This requires developing analytical assays for quantifying ribociclib monitoring in rat plasma. We present a fully validated, sensitive, and simple LC‐MS/MS method for measuring ribociclib in rat plasma. Ribociclib‐D6 was utilized as an internal standard, and a simple protein precipitation procedure with acetonitrile was used in sample preparation. Excellent assay linearity was observed over a standard curve concentration of 1.008–1027.624 ng/mL. Acceptable intra‐ and inter‐day accuracy and reproductivity were demonstrated for ribociclib quality controls (bias and CV% within ±15%). Complete extraction recovery of ribociclib was achieved, and a negligible matrix effect of analyte to internal standard ratio was observed. Ribociclib was stable at various conditions, including bench‐top, freeze–thaw, and short‐term stability. Overall, the presented method is simple, sensitive, accurate, and precise and was successfully applied to quantify ribociclib in plasma samples from a pharmacokinetic study of ribociclib suspension and nanoparticle formulation in rats.