Determination of 2,3-dihydro-6-[3-(2-hydroxymethyl)phenyl-2-propenyl]-5-benzofuranol in plasma using liquid chromatography with electrochemical detection.
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.
Matuszewski
B K
BK
Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
Constanzer
M L
ML
Bayne
W F
WF
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood* / Q000493:pharmacokinetics; D001572:Benzofurans / Q000097:blood* / Q000493:pharmacokinetics; D001768:Blister / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004563:Electrochemistry; D006801:Humans; D011565:Psoriasis / Q000097:blood; D013056:Spectrophotometry, Ultraviolet
D000893:Anti-Inflammatory Agents; D001572:Benzofurans; C053727:L 651896