To establish a quantitative single-photon emission tomography (SPET) procedure for imaging CNS D2 dopamine receptors, measurement of unchanged iodine-123 iodobenzamide (123I-IBZM) (a selective D2 ligand) in human plasma was investigated. There are three possible radioactive components in human plasma: hydrophilic compounds (iodide ion, etc.), lipophilic metabolites, and unchanged IBZM. Based on the difference in lipophilicity of IBZM and its lipophilic metabolites (LM), a new quantitative method of analysis of 123I-IBZM using a simple solvent extraction was developed. The selective extraction was achieved with n-octane/phosphate buffer (0.1 M, pH 7.4). Extraction efficiency was 93.2% +/- 0.3% (n = 15) for IBZM from plasma, while 99.3% +/- 0.2% (n = 12) of LM remained in the aqueous plasma fraction. Twenty-one confirmation tests with plasma containing known ratios of IBZM/LM, ranging between 0.39 and 7.60, were performed. The experimental results were very close to the values of the true ratios over the wide range (accuracy approximately 99%, relative standard error 6.6%). The data from this simplified method are comparable to those obtained by the high-performance liquid chromatography method. This improved method provides an easy and accurate way to quantify unchanged IBZM in human plasma. With appropriate kinetic modeling and in conjunction with a dedicated SPET imaging device for measuring quantitative information, it may be possible to develop a practical method for measuring D2 receptor density in vivo.