High-performance liquid chromatographic method for simultaneous determination of enantiomers of 5-dimethylsulphamoyl-6,7-dichloro-2-dihydrobenzofuran-2, carboxylic acid and its N-monodemethyl metabolite in monkey plasma and urine after chiral derivatization.
A quantitative method for the simultaneous high-performance liquid chromatographic (HPLC) resolution and determination of the enantiomers of 5-dimethylsulphamoyl-6,7-dichloro-2,3-dihydrobenzofuran-2-carboxyl ic acid, a new diuretic, and its N-monodemethylated metabolite in monkey plasma and urine is described. The method includes diethyl ether extraction of the samples and S-(-)-alpha-methylbenzylamide derivatization of the extract, followed by reversed-phase solid-phase extraction and injection of the resulting diastereoisomers onto a reversed-phase HPLC column. Baseline separation was obtained. The assay showed linearity over the range 0.1-50 micrograms/ml of plasma and 0.25-500 microliters of urine, with a lower limit of detection of ca. 0.01 micrograms/ml for each of the enantiomers. The method is adequate for pharmacokinetic and enantioselective disposition studies of both the diuretic and its metabolite.
Nakano
M
M
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Kawahara
S
S
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D004232:Diuretics / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine; D007700:Kinetics; D008252:Macaca fascicularis; D013237:Stereoisomerism; D013449:Sulfonamides / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine
D004232:Diuretics; D013449:Sulfonamides; C052960:S 8666