The use of simvastatin (SV) increases along with the increasing number of patients with hyperlipidemia and cardiovascular disease risk factors. Consequently, this condition leads to the increasing need of analytical determination of SV in blood plasma. Analysis of SV in human plasma using protein precipitation method and HPLC with UV detector has not been reported. This research was purpose to find out the rapid, accurate, and valid of SV analysis method in human plasma. In this research plasma samples were treated with protein precipitation method. The analyte was then analyzed using HPLC with C18 column 250x4 mm and 5 µm of particle size, the mobile phase contained of phosphate buffer 0.01 M (pH 4.0) and acetonitrile 30:70 v/v with flow rate 1 mL/minute, and detected at 239 nm. The analysis method was validated based on some parameters, such as selectivity, accuracy, precision, repeatability, linearity, LOD, LOQ, and system suitability. The result showed selectivity represented by Rs was 2.870, repeatability by its CV less than 2%, and linearity by its coefficient correlation (r) 0.9992 for concentration range 0.08-0.32 ppm. Based on chromatogram peak area, LOD and LOQ were 0.0132 and 0.0440 ppm respectively, accuracy and precision were 86.25-89.36% and 0.66-1.81% were obtained. The result of system suitability test from retention time and chromatogram peak area showed by its CV less than 2%. The analysis method was proved to be valid for SV analysis in human plasma
