A highly sensitive, accurate and rapid analytical method based on reversed-phase liquid hromatography/ electrospray ionization tandem mass spectrometry (RP-LC-ESI-MS/MS) has been developed and validated for the determination of Domperidone in human plasma using Atorvastatin as an internal standard (IS). The method was validated over a linear range of 0.101 – 30.300 ng/ml, R2 0.9983. After addition of IS, analytes were extracted from the plasma samples by liquid-liquid extraction using tert-butylmethyl ether. Chromatographic separations were achieved reversed phase column (ACE C18 (50 x 4.6) mm, 3 m particle size) using a mobile phase consisting of formic acid in water (0.1%) and acetonitrile (25: 75, v/v (%)), flow rate 0.50 (mL/min.). Detection utilized a tandem MS/MS, the analytes were ionized using an ESI source in the positive ion mode prior to detection by Multiple Reaction Monitoring (MRM) mode. The analytes were monitored at the following transitions (m/z) 426.2 → 175.1 for Domperidone and (m/z) 559.5 → 440.4 for Atorvastatin respectively. The proposed method was fully validated in terms of linearity, accuracy, precision, specificity, sensitivity, recovery and stability, giving results within the acceptable range.