Bioanalysis by LC-MS/MS and Preclinical Pharmacokinetic Interaction Study of Ribociclib and Oleanolic Acid

Background: Ribociclib (RIBO), approved in 2017 for HR-positive and HER-2-negative metastatic breast cancer treatment is reported to have the potential to induce hepatobiliary toxicity in patients. Oleanolic acid (OLA) has hepatoprotective potential that can be beneficial if coadministered with RIBO. Methodology & results: The primary scope of this study was to develop quantitative bioanalytical methods for RIBO and OLA. Two methods (for +ve electrospray ionization [ESI] and -ve ESI) were developed and validated according to USFDA bioanalytical guidelines. Discussion/conclusion: A single and simple sample preparation method was developed with >75% recovery. The accuracy and precision for RIBO and OLA were within acceptable limits over the calibration range of 5-500 ng/ml. This work reports, for the first time, the drug-drug interaction potential between RIBO and OLA.