A rapid and simple high performance liquid chromatography(HPLC) method with a UV detection(241 nm) was developed and validated for estimation of eplerenone from spiked human plasma.The analyte and the internal standard(valdecoxib) were extracted with a mixture of dichloromethane and diethyl ether.The chromatographic separation was performed on a HiQSil C-18HS column(250 mm 4.6 mm,5 μm) with a mobile phase consisting of acetonitrile:water(50:50,v/v) at flow rate of 1 mL/min.The calibration curve was linear in the range 100-3200 ng/mL and the heteroscedasticity was minimized by using weighted least squares regression with weighting factor 1/X. A rapid and simple high performance liquid chromatography (HPLC) method with a UV detection (241 nm) was developed and validated for estimation of eplerenone from spiked human plasma. The analyte and the internal standard (valdecoxib) were extracted with a mixture of dichloromethane and diethyl ether. The chromatographic separation was performed on a HiQSil C-18HS column (250 mm 4.6 mm, 5 μm) with a mobile phase consisting of acetonitrile: water (50:50, v / v) at flow rate of 1 mL / min The calibration curve was linear in the range 100-3200 ng / mL and the heteroscedasticity was minimized by using weighted least squares regression with weighting factor 1 / X.