A simple, rapid and sensitive liquid chromatography / electro spray ionization tandem mass spectrometry (LC–ESI–MS/MS) assay method has been proposed for the determination of apremilast in human plasma samples using apremilast d5 as internal standard (IS). Analyte and the IS were extracted from the 200 µL of human plasma via simple solid–phase extraction. The Chromatographic separation was obtained on a C18 column operating at a flow rate of 1.0 mL/min by using a mobile phase comprising of mixture of 5mm ammonium acetate in 0.2% formic acid buffer (15:85, v/v) and acetonitrile. A linear (r2 ³ 0.99) of the calibration curve was obtained over the concentration range of 2.03–808 ng/mL.  As per FDA guidelines method validation was performed and the results met the acceptance criteria. The intra–day and inter–day precision (%CV) and accuracy results in five validation batches across five concentration levels were well within the acceptance limits. To analyze the more number of samples in short time, thus increasing the productivity a short run time of 2.25 min for each sample was applied and this was made possible. The method was successfully applied to a pharmacokinetic study in humans.