LC–MS/MS Method Assay for Simultaneous Determination of the Apixaban and Metformin in Rat Plasma: Assessment of Pharmacokinetic Drug–Drug Interaction Study.

This article focuses on the development and validation of a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the simultaneous quantification of apixaban (APB), an oral anticoagulant, and metformin (MET), a hypoglycemic agent, in rat plasma to investigate their pharmacokinetic drug–drug interactions (DDI). The validated method demonstrated acceptable selectivity, linearity, precision, accuracy, recovery, matrix effects, and stability according to FDA and EMA guidelines. Pharmacokinetic studies in rats revealed significant alterations in parameters such as area under the curve (AUC), half-life (t₁/₂), clearance (CL), and maximum concentration (Cmax) when APB and MET were co-administered, suggesting potential DDIs possibly mediated by transporters including organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATE1, MATE2-K). These findings provide preliminary evidence relevant to the concurrent clinical use of APB and MET, particularly in diabetic patients requiring anticoagulation therapy after hip or knee replacement.