In the present work, a rapid, sensitive, specific, precise and accurate liquid chromatography-tandem mass spectrometry method for determination of Osimertinib in human plasma was developed and validated with a large calibration curve range (10-4000 pg/mL) which can be used for routine drug analysis and bioequivalence studies. Liquid-liquid extraction method was used to extract the analyte from the human plasma. The separation was achieved using Xbridge Zorbax Eclipse XDB - C18 (150 x 4.6 mm, 5 μ) column with Acetonitrile: 20mM Ammonium formate (pH-3.0) (50: 50, v/v) as a mobile phase. A flow rate of 1.0 mL/min, no splitting and run time 10.0 min was used for the chromatographic analysis of Osimertinib. Sensitivity of this method was found to be 10 pg/mL. The analyte was analyzed by mass spectrometry in the multiple reaction monitoring mode. A Turbo-Ion spray source was interfaced between the HPLC and triple quadrupole mass spectrometer (MDS Sciex API 4000). Where the acquired masses for osimertinib were 499.6  72.0 m/z and osimertinib -D3 was 503.63  72.0 m/z were used for quantification of an analyte and its IS. The method was validated in terms of accuracy, precision, selectivity, recovery, freeze-thaw stability, bench-top stability, stock solution stability and re-injection reproducibility. The within and between-batch precision was obtained within the range 0.31 to 8.55 and 0.26 to 6.16. The mean recovery for drug was obtained 87.79%, where as the mean recovery of IS was 84.97%. The %RSD value at higher concentration and lower concentration in all stability experiments was within 15%. This method is free from ion suppression, ion enhancement and any type of abnormal ionization.