A new method has been developed to extract 8-methoxypsoralen (8-MOP) from human plasma and to prepare samples for high performance liquid chromatography (HPLC) analysis. Plasma samples are passed through solid phase extraction cartridges that are essentially HPLC "microcolumns" consisting of a bonded silica sorbent that, after activation, selectively retain 8-MOP and then release it when exposed to an eluting solvent. The 8-MOP collected from the cartridge is analyzed by reversed phase HPLC. With this new technique, the 8-MOP is completely recovered and as little as 10 ng/ml can be detected in a 1-ml plasma sample. The average plasma level in a series of 17 patients who had ingested Oxsoralen (approximately 0.6 mg/kg) was 117 ng/ml (+/- 79).