Determination of the thromboxane synthetase inhibitor 6-(1-imidazolylmethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid (DP-1904) in human plasma and urine using solid-phase extraction and high-performance liquid chromatography.
A high-performance liquid chromatographic method for the determination of 6-(1-imidazolylmethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid hydrochloride hemihydrate (DP-1904), a potent and long-acting thromboxane synthetase inhibitor, in human plasma and urine has been developed. DP-1904 and an internal standard were extracted from plasma and urine by means of a Sep-Pak C18 cartridge. The methanol eluate was evaporated and the residue was chromatographed on a reversed-phase column using tetrahydrofuran-0.5% potassium dihydrogen phosphate solution (pH 3.0) (1:16) as the mobile phase at a flow-rate of 1.2 ml/min. Ultraviolet detection at 240 nm resulted in limits of detection of 50 ng/ml for plasma and 1.0 microgram/ml for urine. The method showed satisfactory accuracy and precision. The method was applied to the determination of DP-1904 in plasma and urine samples from a normal human volunteer who had received a 200-mg oral dose of the drug. DP-1904 was rapidly absorbed from the gastrointestinal tract and had a half-life of ca. 30 min. The primary route of elimination was renal, with ca. 60% of the dose being excreted in the urine in the unchanged form within 48 h.