ASSAY OF GLYCERYL TRINITRATE, ISOSORBIDE DINITRATE, AND THEIR METABOLITES IN PLASMA BY LARGE-BORE CAPILLARY COLUMN GAS-LIQUID-CHROMATOGRAPHY

Two large‐bore capillary columns, one with dimethyl polysiloxane (HP‐1®) as the stationary phase and the other with phenyl (50 per cent) methyl (50 per cent) polysiloxane (DB‐17), were used to develop gas‐liquid chromatographic (GLC) assays for measuring isosorbide dinitrate (ISDN), glyceryl trinitrate (GTN), and their metabolites. ISDN, isosorbide‐2‐mononitrate (2‐ISMN), and isosorbide‐5‐mononitrate (5‐ISMN) in plasma, ranging in concentration from 1 to 300 nM, and GTN, glyceryl‐1,2‐dinitrate (1,2‐GDN). and glyceryl‐1,3‐dinitrate (1,3‐GDN), ranging in concentration from 3 to 60 nM in plasma, were analysed on both columns. GLC analysis yielded baseline resolution of the analytes. The method using the dimethyl polysiloxane column gave a lower limit of detectability for GTN of 0·75 nM (signal/noise (s/n) = 2), and the procedure using the phenyl‐methyl column provided a lower limit of detectability for ISDN of 81 pM (s/n = 2). The large‐bore column GLC procedures exhibited shorter retention times for both ISDN and GTN than those previously reported for capillary‐column assays. The chromatographic resolution of analytes and column efficiency of the large‐bore capillary columns were comparable to the results previously found using capillary‐column GC. The assays for ISDN and GTN have been shown to be appropriate for pharmacokinetic studies in volunteers and patients. We determined that the HP‐1® column is appropriate for the analysis of GTN and metabolites, and the DB‐17 column is suitable for analysis of ISDN and its metabolites. We conclude that the use of large‐bore capillary columns provides rapid and reliable GLC assays for organic nitrates. Copyright © 1990 John Wiley & Sons, Ltd.