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Tandem Mass Spectrometry for the Quantification and Bioavailability Test of Nicorandil in Human Plasma  

Moon Chul-Jin (Institute of Metabolism, Green Cross Reference Laboratory)
Lee Eun-Hee (Institute of Metabolism, Green Cross Reference Laboratory)
Yang Song-Hyun (Institute of Metabolism, Green Cross Reference Laboratory)
Moon Hae-Ran (Institute of Metabolism, Green Cross Reference Laboratory)
Publication Information
YAKHAK HOEJI / v.49, no.3, 2005 , pp. 225-229 More about this Journal
Abstract
A rapid, sensitive and selective tandem mass spectrometric method (LC-MS/MS) for the quantitation of nicorandil in human plasma was developed. A bioavailability study of Sigmat tablet (5 mg nicorandil, Choongwae Co.) was per-formed using the validated LC-MS/MS method. The dose of 5 fig of nicorandil (1 tablet) was orally administered to 9 healthy Korean subjects. After administration, blood was taken at 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, and 24 hour. The validation data were as follows; the standard curve was linear ($r^2$=0.999) over the concentration range of $0.5\~200.0 ng/ml$. The coefficient of variation for intra- and inter-day assay were $3.55\~7.44$, and $2.17\~9.102\%$, respectively. The lower limit of quantification for nicorandil was 0.5 ng/ml. The pharmacokinetic parameters obtained were as follows; $AUC_t$ was 145.9$\pm$83.0 ng-hr/ml, Cmax was 83.8$\pm$32.2 ng/ml, $C_{max}$ was 0.42$\pm$0.13 hr, $K_e$ was 0.56$\pm$0.23 l/hr, and $t_{l/2}$ was 1.42$\pm$0.52 hr. Based on the validated analytical method and pharmacokinetic parameters, a standard guideline of the bioavailability test of nicorandil dos-age forms was prepared successfully and could be used for the bioequivalence test of nicorandil preparation.
Keywords
tandem mass spectrometry; nicorandil; bioavailability;
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