Analytical Methods for the Determination of Apixaban in Pharmaceuticals and Biological Matrices: A Systematic Review.

Apixaban (APX) is a direct oral anticoagulant (DOAC) developed by Bristol Myers Squibb and Pfizer for the prevention of stroke and systemic embolism in patients with non valvular atrial fibrillation (NVAF), as well as for the prophylaxis of deep vein thrombosis (DVT) and the reduction of recurrent DVT and pulmonary embolism risk following initial therapy. This paper provides a comprehensive review of physicochemical properties of APX and the analytical methodologies for its quantification in bulk drug, pharmaceutical formulations, and in biological fluids. The analytical methods reported to date have been summarized, with an emphasis on major techniques such as spectrophotometry, and reverse-phase high performance liquid chromatography (RP-HPLC) coupled to ultraviolet (UV) detection or mass spectrometry (MS). Sample pretreatment methods for the analysis of biological matrices have also been systematically discussed. Additionally, the "whiteness" of the reported methods for the determination of APX in biological matrix are assessed according to the RGB 12 algorithm.