Determination of isosorbide dinitrate biotransformation in various tissues of the rabbit by capillary column...

A selective and sensitive capillary column gas-liquid chromatographic procedure has been developed for the simultaneous determination of isosorbide dinitrate (ISDN) and its mononitrate metabolites in rabbit blood and tissue homogenates. The method has a limit of detection of 0.1 ng ml-1 for ISDN, 1 ng ml-1 for isosorbide 5-mononitrate (5-ISMN), and 2 ng ml-1 for isosorbide 2-mononitrate (2-ISMN). The day-to-day coefficients of variation were 2.5, 6.8, and 11.3 per cent for ISDN, 5-ISMN, and 2-ISMN, respectively. The within-day coefficients of variation were 2.7, 4.9 and 6.5 per cent for ISDN, 5-ISMN, and 2-ISMN, respectively. The procedure was used to determine the biotransformation of ISDN (2 X 10(-7) M) to 5-ISMN and 2-ISMN by various rabbit tissue homogenates. The relative rate of biotransformation of ISDN was liver greater than lung approximately equal to intestine greater than kidney greater than blood approximately equal to skeletal muscle, with the lung and intestine homogenates being about two-thirds as active as liver homogenates. These results indicate that extrahepatic biotransformation of ISDN, especially by lung and intestine, may contribute to the systemic clearance of ISDN in the rabbit.