Insights Into the Complexities of Antithrombotic Interactions: A Core–Shell Particle‐Based UHPLC–MS/MS Method to Investigate Dexamethasone's Influence on Apixaban and Rivaroxaban Pharmacokinetics

ABSTRACT The implementation of core–shell particles in HPLC has many advantages in analytical methodologies, including enhancement of sensitivity and resolution. Moreover, high flow rates and short analysis times could be used to achieve efficient separations. A sensitive and specific UHPLC–MS/MS method was developed and validated for the simultaneous quantification of apixaban (APX) and rivaroxaban (RVX) in rat plasma. This validated method was designed to investigate the potential pharmacokinetic (PK) interactions between dexamethasone (DEX) and both cited drugs in rat model. Separation and validation were performed utilizing a C18 Poroshell 120EC (50 mm × 4.6 mm, 2.7 µm) column with a mobile phase of methanol:water with 0.1% formic acid (95:5, v/v) eluted in an isocratic mode at 0.3 mL/min flow rate. Liquid–liquid extraction method was employed to extract the cited drugs from rat plasma using diethyl ether:dichloromethane (70:30, v/v). The procedure was carried out utilizing positive ionization and multiple reaction monitoring mode (MRM) for the detection of the drugs and the internal standard, moxifloxacin. The bioanalytical method was validated using US‐Food and Drug Administration and European Medicines Agency guidelines in terms of selectivity, linearity, accuracy, precision, recovery, dilution integrity, matrix effect, stability, and carryover. On the basis of the findings of the PK study in rat model, a potential drug–drug interaction was observed between DDI and the cited antithrombotic medications that may lead to a decrease in their plasma concentrations. As a result, these findings can be utilized for further clinical investigation.