Simultaneous determination of glyceryl trinitrate and its principal metabolites, 1,2- and 1,3-glyceryl dinitrate, in plasma by gas chromatography-negative ion chemical ionization-selected ion monitoring.

A specific and sensitive method for the quantitation of glyceryl trinitrate (GTN) and its principal metabolites, 1,2- and 1,3-glyceryl dinitrate (GDN) in dog plasma by capillary gas chromatography-negative ion chemical ionization-selected ion monitoring using dichloromethane as a reagent gas and the corresponding compounds labelled with stable isotopes as internal standards. The quantitation limits of the method for GTN and the GDNs were 0.1 and 1.0 ng/ml in plasma, respectively. When GTN was administered intravenously to four anaesthetized beagle dogs at a dose of 6 micrograms/kg . min for 30 min, the plasma levels of GTN and 1,2- and 1,3-GDN reached a maximum at the end-point of infusion and decreased with bi-exponential decay. The half-lives of the alpha- and beta-phases were 0.50 and 4.95 for GTN, 8.10 and 40.6 for 1,2-GDN and 8.50 and 48.5 for 1,3-GDN, respectively.