Determination of nicorandil in plasma using high-performance liquid chromatography with photoconductivity and ultraviolet detection. Application to pre-clinical pharmacokinetics in beagle dogs.
A sensitive and precise method for the determination of nicorandil, a new anti-anginal medication, is reported. The method involves solid-phase extraction of the drug and internal standard using Bond-Elut C18 extraction columns, reversed-phase high-performance liquid chromatography on a Zorbax-Phenyl column and detection with photoconductivity and ultraviolet detection in series. Photoconductivity, performed with the Tracor 965 photoconductivity detector, provided a limit of detection of 2 ng/ml in plasma (between-day coefficient of variation of 15%) but the linear range of response was limited to only about 100 ng/ml. Ultraviolet detection in series with the photoconductivity detector extended the linear range of the analytical system to 1000 ng/ml (coefficient of variation 4.4%). The utility of the method is demonstrated in a dog pharmacokinetic study in which a 5-mg intravenous dose was compared to a 10-mg oral solution dose in six beagle dogs. The oral solution was absorbed rapidly, achieving an average maximum concentration of 857 ng/ml in 11.2 min. The absolute bioavailability of nicorandil in dogs in this study was determined to be 84.2%.
Schwende
F J
FJ
Drug Metabolism Research, Upjohn Company, Kalamazoo, MI 49001.
Lewis
R C
RC
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D020108:Nicorandil; D010783:Photometry; D014466:Ultraviolet Rays; D014665:Vasodilator Agents / Q000097:blood* / Q000493:pharmacokinetics
D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil