title: Simultaneous quantitation of nicorandil and its denitrated metabolite in plasma by LC-MS/MS: application for a pharmacokinetic study.
abstract: 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.
authors: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil. isaccesar@bol.com.br
authors: Isabela Costa
authors: IC
authors: César
authors: Leandro Francisco Silva
authors: LF
authors: Bastos
authors: Adriana Martins
authors: AM
authors: Godin
authors: Márcio de Matos
authors: Mde M
authors: Coelho
authors: Débora Pereira
authors: DP
authors: Araujo
authors: Ângelo
authors: Â
authors: de Fátima
authors: Patrícia Alves Maia
authors: PA
authors: Guidine
authors: Gerson Antônio
authors: GA
authors: Pianetti
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D020108:Nicorandil / Q000097:blood* / Q000493:pharmacokinetics; D011342:Procainamide / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D009536:Niacinamide; D020108:Nicorandil; C030731:N-(2-hydroxyethyl)nicotinamide; D011342:Procainamide