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

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.