Improved automated simultaneous determination of isosorbide dinitrate and its metabolites in plasma by capillary column gas chromatography

An automated specific and sensitive method for the simultaneous determination of isosorbide dinitrate and its metabolites isosorbide‐2‐mononitrate, isosorbide‐5‐mononitrate, isomannide mononitrate, and isoidide mononitrate at concentrations down to 0.5, 1, 3, 2, and 2 ng/ml, respectively, in human plasma is described. The procedure involves the extraction of the drug and its metabolites together with their internal standards isomannide dinitrate and o‐nitrobenzyl alcohol from plasma with dicholromethane. The analysis is carried out by fused silica capillary gas chromatography using a 63Ni‐electron capture detector. The method is applied to the pharmacokinetics of isosorbide dinitrate in humans.