PLASMA-LEVELS OF 8-METHOXYPSORALEN DETERMINED BY HIGH-PRESSURE LIQUID-CHROMATOGRAPHY IN PSORIATIC PATIENTS INGESTING DRUG FROM 2 MANUFACTURERS

[摘要] A rapid and sensitive high-pressure liquid chromatographic technique (HPLC) was adapted to measure plasma levels of 8-methoxypsoralen (8-MOP) in 22 psoriatic patients receiving photochemotherapy with 8-MOP and long-wave ultraviolet light (PUVA). 1 ml plasma samples containing ammidin as an internal standard are extracted with benzene. After evaporation under nitrogen the residue is redissolved in methylenechloride:acetonitrile, 95:5, and chromatographed using a normal phase HPLC system with a 10 .mu. silica particle column and a UV detector at 254 nm. The sensitivity of the method is 10 ng/ml plasma. Plasma concentrations of 8-MOP were measured between 2 and 4 h after ingestion of therapeutic doses of 8-MOP provided by 2 manufacturers. Mean 8-MOP plasma levels were 27 .+-. 35 ng/ml plasma 2 h after ingestion of the only drug presently available on the U.S. market, 8-MOP (Elder). These values were significantly below (P < 0.001) those obtained with 8-MOP (Roche) which were 104 .+-. 79 ng/ml plasma. A number of patients on 8-MOP (Elder) did not have detectable levels of 8-MOP 2 h after ingestion. The time course patterns also differed, possibly indicating a slower and less complete absorption for 8-MCP (Elder). Repeated time course studies in the same patient were reproducible although the absolute concentrations showed some variation. Preliminary evidence indicates that the plasma levels of 8-MOP have therapeutic relevance.