Determination of isosorbide dinitrate and its mononitrate metabolites in human plasma using Extrelut purification and capillary column gas-liquid chromatography.

A rapid, accurate and sensitive method for the determination of isosorbide dinitrate (internal standard: isomannide dinitrate) and its 2- and 5-mononitrate metabolites (internal standard: isoidide mononitrate) in 1.0 ml of human plasma has been developed. Before chromatographic quantitation by gas-liquid chromatography with electron-capture detection, isosorbide nitrates were purified by Extrelut chromatography (recovery about 90%), eliminating most of the endogenous interferences. Routine limit of quantitation and reproducibility were 0.5, 2.0 and 10.0 ng/ml and 6, 8 and 7% for isosorbide dinitrate and the 2- and 5-mononitrates, respectively. This method allowed the behaviour of this vasodilating drug and its metabolites to be studied in humans.