A liquid chromatography‐electrospray ionization tandem mass spectrometry method was developed and validated for the simultaneous quantitation of nicorandil and its denitrated metabolite, N‐(2‐hydroxyethyl)‐nicotinamide, in rat plasma. After a liquid–liquid extraction step, chromatographic separation was performed on a ShinPack C~18~ column with an isocratic mobile phase composed of methanol and 2 mM aqueous ammonium acetate containing 0.03% (v/v) formic acid (33:67 v/v). Procainamide was used as an internal standard (IS). Selected reaction monitoring was performed using the transitions m/z 212 → m/z 135, m/z 166 → m/z 106 and m/z 236 → m/z 163 to quantify nicorandil, its denitrated metabolite and IS, respectively. Calibration curves were constructed over the range of 5–15 000 ng.ml^−1^ for both nicorandil and its metabolite. The mean relative standard deviation (RSD%) values for the intra‐run precision were 5.4% and 7.3% and for the inter‐run precision were 8.5% and 7.3% for nicorandil and its metabolite, respectively. The mean accuracy values were 100% and 95% for nicorandil and its metabolite, respectively. No matrix effect was detected in the samples. The validated method was successfully applied to a pharmacokinetic study after per os administration of nicorandil in rats. Copyright © 2011 John Wiley & Sons, Ltd.