Quantitative determination of isosorbide dinitrate and two metabolites in plasma

A GLC method for the determination of plasma isosorbide dinitrate and two metabolites, isosorbide 2-mononitrate and isosorbide 5-mononitrate, is described. The three substances are extracted from alkalinized plasma with ether. Quantitation is effected by electron-capture detection after GLC separation with a 30% SE-30 column. The unusually heavy liquid phase loading is necessary to eliminate irreversible adsorption on the solid support. The electron-capture detector provides excellent sensitivity and specificity because of the electronegative nature of the nitric ester. The method was used to study the blood levels of isosorbide dinitrate and two metabolites in four beagle dogs after single oral doses of 40 mg of isosorbide dinitrate and in two human volunteers after a sublingual dose of 10 mg of isosorbide dinitrate.