Determination of the Antiplatelet Agent, KB-3022,and Its Metabolite by High-Performance Liquid Chromatography

概要

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A rapid, accurate and reproducible high-performance liquid chromatographic method for the simultaneous determination of a new antiplatelet agent, ethyl 2-[4.5-bis(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate (KB-3022), and its main metabolite, 2-[4,5-bis(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetic acid (desethyl KB-3022), in biological fluids has been developed. KB-3022 and desethyl KB-3022 in plasma or urine were extracted with a mixture of n-hexane and dichloromethane (1 : 1), separated on a reversed-phase C_<18> column with a mixture of 0.01M (NH_4)_2HPO_4 (pH3.0), acetonitrile and isopropyl alcohol as a mobile phase, and quantitated by ultraviolet absorbance measurement at 340nm. 4-[2-{4,5-bis(4-methoxyphenyl)thiazol-2-yl}pyrrol-1-yl]butyric acid was used as an internal standard. The detection limit of KB-3022 in plasma was 3ng/ml, and that of KB-3022 in urine and desethyl KB-3022 in plasma or urine was 1ng/ml. The coefficients of variation for the determination of KB-3022 or desethyl KB-3022 in plasma or urine were below 5.6%. This method was applied to the determination of the plasma concentration of KB-3022 and desethyl KB-3022 after intravenous administration to rats.
公益社団法人日本薬学会の論文
1990-04-25