Tandem Mass를 이용한 혈중 니코란딜의 정량법 개발 및 생체이용률시험

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

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 performed using the validated LC-MS/MS method. The dose of 5 mg 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 (γ2=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 2.17~9.10%, respectively. The lower limit of quantification for nicorandil was 0.5 ng/ml. The pharmacokinetic parameters obtained were as follows; AUCt was 145.9±83.0 ng.hr/ml, Cmax was 83.8±32.2 ng/ml, tmax was 0.42±0.13 hr, Ke was 0.56±0.23 1/hr, and t1/2 was 1.42±0.52 hr. Based on the validated analytical method and pharmacokinetic parameters, a standard guideline of the bioavailability test of nicorandil dosage forms was prepared successfully and could be used for the bioequivalence test of nicorandil preparation.