Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil.
J Mass Spectrom. 2011 Nov;46(11):1125-30. doi: 10.1002/jms.1998.
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.
建立并验证了一种用于同时定量测定大鼠血浆中硝酸异山梨酯及其去硝化代谢物 N-(2-羟乙基)烟酰胺的液相色谱-电喷雾串联质谱法。经过液-液萃取步骤后，采用甲醇和 2 mM 氨水中含有 0.03%（v/v）甲酸（33:67 v/v）的等度流动相在 ShinPack C(18)柱上进行色谱分离。普鲁卡因胺用作内标（IS）。使用过渡质荷比 m/z 212→m/z 135、m/z 166→m/z 106 和 m/z 236→m/z 163 进行选择反应监测，分别定量测定硝酸异山梨酯、其去硝化代谢物和 IS。硝酸异山梨酯及其代谢物的校准曲线范围均为 5-15,000 ng.ml(-1)。内运行精密度的平均相对标准偏差（RSD%）值分别为 5.4%和 7.3%，外运行精密度的平均相对标准偏差（RSD%）值分别为 8.5%和 7.3%。硝酸异山梨酯及其代谢物的平均准确度值分别为 100%和 95%。在样品中未检测到基质效应。该验证方法成功应用于大鼠口服给予硝酸异山梨酯后的药代动力学研究。
