HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC METHOD FOR STABILITY AND PHARMACOKINETIC STUDIES OF NICORANDIL

Nicorandil is a unique vasodilator that combines the actions of a pota ssium channel activator and a nitrovasodilator. Little literature is a vailable 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 mu g/ml with 180-mul samples. Nicorandil was found to be relatively stabl e 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 degra dation and in vivo metabolism produced N-(2-hydroxyethyl)nicotinamide, the denitrated product. Preliminary pharmacokinetic investigations sh owed that the assay is capable of quantitating nicorandil in rat plasm a over a range of 0.3-100 mug/ml. These studies also suggested that th e pharmacokinetics of nicorandil are dose-dependent.