Simultaneous Quantification of Abemaciclib and Letrozole in Rat Plasma: Method Development, Validation and Pharmacokinetic Application

Treatment through a combination of drugs involving cyclin D-dependent kinase inhibitors like abemaciclib and aromatase inhibitor like letrozole proved to be a potential therapeutic regimen and first-line treatment in estrogen receptor-positive breast cancer. In this study, we developed a simple and simultaneous RP-HPLC bioanalytical method for quantifying abemaciclib and letrozole in rat plasma. Abemaciclib and letrozole were separated on Zorbax Eclipse C column employing a gradient elution method comprising 10 mM ammonium acetate (pH 5) and acetonitrile as mobile phase. The method was found to have acceptable selectivity, accuracy (97.20-118.17%), precision (1.10-9.39%) and stability in the validation experiment performed as per the US Food and Drug Administration guidelines. The method sensitivity was low at a concentration level of 100 ng/ml. The applicability of the method has been verified through a single-dose oral pharmacokinetic study in rat. The developed method will be useful to quantitate the analytes in rat plasma samples of different preclinical studies including their pharmacokinetic drug-drug interactions in the future. To date, no method has been reported for the quantification of abemaciclib and letrozole simultaneously in any type of biological matrices. Therefore, this study makes a definite significant contribution in the field of bioanalytical research.