Determination of a new calcium antagonist, sesamodil fumarate (SD-3211), and its metabolite in plasma by liquid chromatography with electrochemical detection.
A sensitive and selective high-performance liquid chromatographic method is described for the determination of a novel calcium antagonist, (+)-(R)-3,4-dihydro-2-[5-methoxy-2-[3-[N-methyl-N-[2-[(3,4- methylenedioxy)phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl-3-oxo-2H- 1,4-benzothiazine hydrogen fumarate (sesamodil fumarate; JAN, SD-3211, I), and its N-desmethylated metabolite (II) in plasma. Compounds I and II and an internal standard were isolated from plasma by solid-phase and liquid-liquid extraction. The extract was chromatographed on a reversed-phase C18 column, and the compounds of interest were detected by dual coulometric electrodes operated in an oxidative screen mode. The limit of determination for both I and II was at least 0.4 ng/ml in plasma. The utility of the assay was demonstrated by determining plasma levels of I and II in five dogs administered an oral dose of 60 mg of the drug.
Morishima
K
K
Central Research Laboratories, Santen Pharmaceutical Co., Ltd., Osaka, Japan.
Tahara
R
R
Horiuchi
M
M
D000818:Animals; D002121:Calcium Channel Blockers / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D004285:Dogs; D004355:Drug Stability; D004563:Electrochemistry; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D011786:Quality Control; D013844:Thiazoles / Q000097:blood* / Q000493:pharmacokinetics
D002121:Calcium Channel Blockers; D013844:Thiazoles; C064356:sesamodil