Packed-column supercritical fluid chromatography for the analysis of isosorbide-5-mononitrate and related a compounds in bulk substance and tablets

We describe a packed-column supercritical fluid chromatographic method that can be used for the analysis of isosorbide-5-mononitrate (5-ISMN) bulk sub stance and the 5-ISMN content of Imdur tablets. The method is based on meth anol-modified carbon dioxide as the mobile phase and porous graphitized car bon (PGC, Hypercarb) as column support at 40 degrees C and 100 bar back pre ssure. The method makes it possible to simultaneously determine 5-ISMN and related compounds. In order to elute NO, with acceptable retention time a q uarternary ammonium hydrogen sulfate salt is added to the methanol modifier . An almost linear increase of the retention time with increasing carbon co ntent of the counter ion was found. Tetramethyl ammonium hydrogen sulfate 5 mM in methanol was used in the final method as polar modifier for the simu ltaneous determination of possible degradation products within 12 min. The present method can separate and detect related compounds such as isosorbide -2,5-dinitrate, isomannidemononitrate and isosorbide-2-mononitrate at the 0 .1% (w/w) level as required by regulatory guidelines. Nitrate can be detect ed down to about 0.02% (w/w). Repeated analyses of ground tablet powder gav e an assay precision for isosorbide-5-mononitrate of 1.4% (R.S.D., eight sa mples and two injections of each). For related substances at an area percen t of 0.1 the precision was less than 10% . (C) 2000 Elsevier Science B.V. A ll rights reserved.