Assay of glyceryl trinitrate, isosorbide dinitrate, and their metabolites in plasma by large-bore capillary column gas-liquid chromatography

✍ Scribed by Brian P. Booth; Brian M. Bennett; James F. Brien; Douglas A. Elliott; Gerald S. Marks; John L. McCans; Kanji Nakatsu

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 636 KB
• Volume: 11
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510110803

✦ Synopsis

Two large-bore capillary columns, one with dimethyl polysiloxane (HPl@) 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-l,2-dinitrate (I,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 (signalhoise (sh) = 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-I@ 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. KEY WORDS Glyceryl trinitrate and dinitrate metabolites metabolites Large-bore capillary columns Gas-liquid chromatographic assay Plasma Isosorbide dinitrate and mononitrate *Canadian Heart Foundation Scholar.