The use of internal-surface reversed-phase (ISRP) chromatography of unprocessed plasma samples was investigated as an alternative method of quantitation of the arterial plasma metabolite time course of [18F]N-methylspiperone. The ISRP method was directly compared to standard solid phase extraction/HPLC (SPE/HPLC) methods currently in wide use. Results indicate that: (1) the ISRP method is rapid and minimizes sample preparation; (2) recovery of radioactivity from the ISRP column is greater than 90%; (3) no radioactivity remains associated with chromatographically size excluded proteins and (4) the quantitative results are well correlated with conventional SPE/HPLC methods.