Determination of 2,3-dihydro-6-[3-(2-hydroxymethyl)phenyl-2-propenyl]-5-benzofuranol in plasma using liquid chromatography with electrochemical detection

Abstract

A reversed-phase column liquid chromatographic (LC) method with electrochemical detection (ED) is described for the quantification of 2,3-dihydro-6-[3-(2-hydroxymethyl)phenyl-2-propenyl]-5-benzofuranol (compound 1), a new locally active dual inhibitor of leukotriene and prostaglandin synthesis, in plasma. After a single liquid-liquid extraction of the biological specimen, the extract was analyzed using a liquid chromatograph with an amperometric detector set at an oxidation potential of +0.55 V. The resulting chromatograms are free from endogenous interference and the limit of detection is 0.2 ng/ml. Several other analogous dihydrobenzofuranols were shown to be electrochemically active, permitting their determination using LC with ED. The described analytical method has been fully validated in the concentration range 0.5-20 ng/ml of plasma and utilized in the analysis of plasma samples from human clinical studies. The analytical methodology has also been adapted for analysis of compound 1 in human skin blister fluid after topical administration of 1.