Determination of nicorandil in plasma using high-performance liquid chromatography with photoconductivity and ultraviolet detection : Application to pre-clinical pharmacokinetics in beagle dogs

• Published in: Journal of chromatography. Biomedical applications Vol. 525; no. 1; pp. 151 - 160
• Main Authors: Schwende, F.J., Lewis, R.C.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 1990; Elsevier
• Subjects: Analysis; Biological and medical sciences; General pharmacology; Medical sciences; Pharmacology. Drug treatments; Antianginal agent; Fissipedia; Carnivora; Vasodilator agent; HPLC chromatography; Ultraviolet spectrometry; Blood plasma; Assay; Vertebrata; Reversed phase chromatography; Mammalia; Photoconducting device; Animal; Extraction; Pharmacokinetics; Dog
• ISSN: 0378-4347
• DOI: 10.1016/S0378-4347(00)83388-5

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® C 18 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%