High-performance liquid chromatographic method for stability and pharmacokinetic studies of nicorandil.
Nicorandil is a unique vasodilator that combines the actions of a potassium channel activator and a nitrovasodilator. Little literature is available on its chemical stability and pharmacokinetics in animals. We developed a simple, specific, sensitive, and precise high-performance liquid chromatographic method for the determination of nicorandil in aqueous solution and rat plasma, achieving a detection limit of 0.3 microgram/ml with 180-microliters samples. Nicorandil was found to be relatively stable between pH 2 and 10 at 37 degrees C (half-life = 461-84 h) and it is subjected to specific base catalysis above pH 10. Both chemical degradation and in vivo metabolism produced N-(2-hydroxyethyl)nicotinamide, the denitrated product. Preliminary pharmacokinetic investigations showed that the assay is capable of quantitating nicorandil in rat plasma over a range of 0.3-100 micrograms/ml. These studies also suggested that the pharmacokinetics of nicorandil are dose-dependent.
Bachert
E L
EL
Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo 14260.
Fung
H L
HL
D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D008954:Models, Biological; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D020108:Nicorandil; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D014665:Vasodilator Agents / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics
D007202:Indicators and Reagents; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil