Determination of the antiplatelet agent. KB-3022, and its metabolite by high-performance liquid chromatography.
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 C18 column with a mixture of 0.01 M (NH4)2HPO4 (pH 3.0), acetonitrile and isopropyl alcohol as a mobile phase, and quantitated by ultraviolet absorbance measurement at 340 nm. 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 3 ng/ml, and that of KB-3022 in urine and desethyl KB-3022 in plasma or urine was 1 ng/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.
Nakada
Y
Y
Pharmaceuticals Research Center, Kanebo, Ltd., Osaka, Japan.
Ikuta
Y
Y
Kawashima
T
T
Awata
N
N
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000032:analysis* / Q000097:blood / Q000652:urine; D011758:Pyrroles / Q000032:analysis* / Q000097:blood / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000032:analysis* / Q000097:blood / Q000652:urine
D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D013844:Thiazoles; C064847:KB 3022; C064848:desethyl KB 3022