Development of a stability-indicating RP-UPLC method for simultaneous determination of Abemaciclib and Olaparib with LC-MS characterization of degradation products and in vitro performance evaluation.

The simultaneous determination of Abemaciclib and Olaparib in in-houseprepared tablets was accomplished by the development and validation of a novel and rapid and sensitive reverse-phase ultra-performance liquid chromatography (RP-UPLC) technique. Using a Waters X-Bridge C18 (4.6 × 100 mm, 3.5 μm) column and a mobile phase made up of 0.1% orthophosphoric acid in water, acetonitrile and methanol (70:20:10% v/v/v) in an isocratic elution mode at a flow rate of 1 mL/min, the chromatographic separation was accomplished. High sensitivity and selectivity were made possible by performing the detection at 219 nm. Following ICH Q2(R1) criteria, the technique was validated and showed high linearity (R2 > 0.999) for both drugs over the concentration range of 10-60 μg/mL. Within acceptable boundaries (<2% Relative Standard deviation (RSD)), both intra-day and inter-day precision and accuracy (recovery percentage) were proven. Forced degradation studies confirmed the method's stability-indicating capability, Stability studies indicated significant degradation under acid, alkali, peroxide and thermal degradation conditions. The degradation products were characterized by LC-MS technique, and possible degradation pathways were proposed. Additionally, in vitro pharmacokinetic evaluation, including dissolution and drug release kinetics, was performed to assess formulation performance. The developed method proved simple, precise and robust, making it suitable for routine quality control, stability study and pharmacokinetic studies of Abemaciclib and Olaparib co-formulated tablets.