The purpose of this research and development was to develop the elevated susceptible, speedy, stable and reproducible extraction method with precise results. At the same time, this method would be efficient in analyzing the large numbers of plasma samples obtained for bioequivalence studies. The chromatography was performed by using column ZIC®-HILIC, 4.6×150 mm, 5µ. Nimodipine was used as internal standard. The solid phase extraction was used to extract Acamprosate and Nimodipine (Internal standard) from plasma samples. The calibration curve was relied on the concentration of 10.01 ng/mL to 709.36 ng/mL for Acamprosate in human plasma Keywords: Bioequivalence study, LCMS and solid phase extraction