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Enantiomeric bioanalysis of simendan and levosimendan by chiral high‐performance liquid chromatography
Author(s) -
Wikberg Tom,
Korkolainen Tapio,
Karlsson Marianne
Publication year - 1996
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1996)8:7<511::aid-chir8>3.0.co;2-d
Subject(s) - chemistry , bioanalysis , levosimendan , enantiomer , chromatography , high performance liquid chromatography , chiral column chromatography , organic chemistry , heart failure , medicine
rac ‐Simendan, (±)‐(R, S)‐[[4‐(1,4,5,6‐tetrahydro‐4‐methyl‐6‐oxo‐3‐pyridazinyl)‐phenyl]hydrazono]propanedinitrile, and the levorotatory enantiomer levosimendan, are drug candidates intended for the treatment of congestive heart failure. An enantiospecific high‐performance 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 β‐cyclodextrin stationary phase in reversed phase mode. With an eluent containing 24–33% 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. © 1996 Wiley‐Liss, Inc.