Enantiomeric bioanalysis of simendan and levosimendan by chiral high-performance liquid chromatography

✍ Scribed by Tom Wikberg; Tapio Korkolainen; Marianne Karlsson

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 725 KB
• Volume: 8
• Category: Article
• ISSN: 0899-0042
• DOI: 10.1002/(sici)1520-636x(1996)8:7<511::aid-chir8>3.0.co;2-d

✦ Synopsis

rat-Simendan, (2)-RS)-[ [4-(1,4,5,&tetrahydro-4-methyl~oxo-3-pyridazinyl)phenyll hydrazonol propanedinitrile, and the levorotatory enantiomer levosimendan, are drug candidates intended for the treatment of congestive heart failure. An enantiospecific highperformance liquid chromatographic (HPLC) method suitable for determination of the ratio of the enantiomer concentrations in blood plasma samples was developed. Direct resolution of the enantiomers was achieved by using a chiral p-cyclodextrin stationary phase in reversed phase mode. With an eluent containing 2433% of methanol in a 0.5% (v/v) triethylammonium acetate buffer, pH 6.0, and a flow rate of 1 ml/min, a resolution (1.2-1.6) adequate for the determinations was achieved. By using UV detection, the relative concentration of the enantiomers in plasma was assessed down to 10 ng/ml. For the racemate, the results indicated a slightly enantioselective disposition and plasma protein binding in rat, dog, and man. The pure enantiomer, levosimendan, was found not to isomerize in vivo. o 1996 Wiley-Liss, Inc.