In order to prepare samples for HPLC analysis with maximum drug recovery and impurity elimination, a revised method for the extraction and purification of a target substance from plasma was developed and applied in a pharmacokinetic study with Nimodipine as a model drug. After protein precipitation of a plasma sample using pure methanol and evaporation of the supernatant to dryness, methanol of various concentrations from 10% to 100% were used to dissolve the remaining residues with the goal of maximizing drug recovery and impurity elimination. Through rigorous screening with HPLC peaks from residual impurity and recovered drug as the criteria, a methanol concentration of 30% was chosen. The standard curve was linear （r2〉 0.999） over the range of 2-160 ng/mL with a limit of quantification （LOQ） of 2 ng/mL. Intra- and inter-day precision values were below 15%, and the accuracy ranged from -1.70% to 5.88% at all three quality control （QC） levels. The wavelength of maximum absorption was 238 nm, and a smaller LOQ value of 2 ng/mL was achieved compared with the reported method. The revised method was successfully applied in a pharmacokinetic study of Nimodipine in rats and sample preparations of lidocaine hydrochloride.
