This research aims to synthesize a specific and efficient sorbent to use in the extraction of apixaban from human plasma samples and its determination by high‐performance liquid chromatography‐tandem mass spectrometry. High specific surface area of metal‐organic framework, magnetic property of iron oxide nanoparticles, selectively of molecular imprinted polymer toward the analyte, and the combination of dispersive solid‐phase extraction method with a sensitive analysis system provided an efficient analytical method. In this study, first, a molecularly imprinted polymer combined with magnetic metal organic framework nanocomposite was prepared and then characterized using different techniques. Then the sorbent particles were used for selective extraction of the analyte from plasma samples. The efficiency of the method was improved by optimizing effective parameters. According to the validation results, wide linear range (1.02–200 ng mL−1), acceptable coefficient of determination (0.9938), low limit of detection (0.32 ng mL−1) and limit of quantification (1.02 ng mL−1), high extraction recovery (78%), and good precision (relative standard deviations ≤ 2.9% for intra‐ (n = 6) and interday (n = 6) precisions) were obtainable using the proposed method. These outcomes showed the high potential of the proposed method for screening apixaban in the human plasma samples.