Determination of isosorbide dinitrate biotransformation in various tissues of the rabbit by capillary column gas-liquid chromatography

✍ Scribed by G. S. Tam; K. Nakatsu; J. F. Brien; G. S. Marks

• Publisher: John Wiley and Sons
• Year: 1987
• Tongue: English
• Weight: 454 KB
• Volume: 8
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510080105

✦ Synopsis

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 O.lng ml-l for ISDN, l n g ml-' for isososorbide 5-mononitrate (5-ISMN), and 2 ng ml-l for isorbide 2-mononitrate (ZISMN). 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 lo-' M) to 5-ISMN and 2-ISMN by various rabbit tissue homogenates. The relative rate of biotransformation of ISDN was liver > lung = intestine > kidney > blood = 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.