Bachert E L, Fung H L
Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo 14260.
J Chromatogr. 1993 Sep 22;619(2):336-41. doi: 10.1016/0378-4347(93)80127-p.
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.
尼可地尔是一种独特的血管扩张剂，它兼具钾通道激活剂和硝基血管扩张剂的作用。关于其在动物体内的化学稳定性和药代动力学的文献较少。我们开发了一种简单、特异、灵敏且精确的高效液相色谱法，用于测定水溶液和大鼠血浆中的尼可地尔，使用180微升样品时检测限为0.3微克/毫升。结果发现，尼可地尔在37℃下pH值为2至10之间相对稳定（半衰期 = 461 - 84小时），在pH值高于10时会发生特定的碱催化反应。化学降解和体内代谢都会产生N - (2 - 羟乙基)烟酰胺，即脱硝基产物。初步药代动力学研究表明，该测定法能够在0.3 - 100微克/毫升的范围内定量大鼠血浆中的尼可地尔。这些研究还表明，尼可地尔的药代动力学具有剂量依赖性。
