Abstract: AIM: To develop an analytical method for quantitation of plasma 5-(4-phenoxybutoxy) psoralen (PAP-1) concentrations after dermal administration in rats by using high-performance liquid chromatography with ultraviolet (HPLC-UV). METHODS: Plasma was extracted by ethyl acetate using isoimperatorin as an internal standard and separated by HPLC on a C₁₈ reversed-phase column using the mobile phase of methanol-water (75∶25,V/V) at a flow rate of 0.8 mL/min. PAP-1 was quantitated using the ratio of the area of the analyte to the area of the internal standard. Plasma concentrations of PAP-1 were determined after dermal administration. RESULTS: The limited of detection was 5.3 μg/L(S/N＞10). Calibration curves were linear over the range of 5.3 to 2120 μg/L. The intra and inter-assay variability ranged from 2.3% to 6.0%, and the accuracy ranged from 102% - 105%, for the low, medium and high quality control samples. The extraction recovery of PAP-1 from plasma was in the range of 83.1% to 86.5%. Following a single dermal dose of 15 mg/kg, the plasma PAP-1 level reached the peak at 4 h. AUC values were 256 and 1209 μg·L^-1·h while C_max values were 74 and 225 μg/L for male and female rats, respectively. CONCLUSION: The method is rapid, specific and sensitive, and can be used to determine plasma concentrations of PAP-1 for pharmacokinetic experiments. PAP-1 exhibits a significant gender differences after dermal administration in rats.

Key words: 5-(4-phenoxybutoxy) psorale (PAP-1), HPLC-UV, Dermal administration, Pharmacokinetics, Gender difference