A novel metal-organic framework (MOF) sorbent based on tannic acid/copper (TA/Cu) was synthesized and characterized for the application of the anticancer drug imatinib (IMA) from biological samples. The TA/Cu MOF was prepared via a facile coordination reaction and thoroughly characterized by SEM, XRD, and FTIR techniques. Critical parameters influencing the extraction efficiency of imatinib mesylate (IMAM), including pH, ionic strength, desorption solvent, and adsorption-desorption time were optimized. With acetonitrile as the desorption solvent, the method demonstrated a broad linear range of 0.55-300 μg L-1 under ideal conditions. Limits of detection and quantification were found to be 0.16 μg L-1 and 0.55 μg L-1, respectively. For plasma samples spiked at clinically relevant concentrations (5, 20, and 50 μg L-1), the sorbent showed good reusability over four cycles and negligible matrix effects. In comparison to previously published methods, the developed dispersive solid phase extraction method based on TA/Cu MOF performed better in terms of simplicity, enrichment factor, and analytical figures. Another objective of this study was to develop a liquid chromatography with tandem mass spectrometry technique that could be commonly and readily used for therapeutic drug monitoring of imatinib following extraction by solid phase extraction (SPE). Therapeutic monitoring applications can reliably quantify IMA in complex biological matrices as a result of the fast dispersive solid phase extraction (DSPE) procedure and environmentally friendly sorbent. For citation: Russol Abdul Salam Faraj, Noor H.K., Saba H. Jamel, Jasim Jamur M.S. LC-MS/MS method for the determination of imatinib mesylate in blood plasma samples after adsorption by copper tannic acid. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2025. V. 68. N 3. P. 27-35. DOI: 10.6060/ivkkt.20256803.7121.