Determination of glyceryl trinitrate in human plasma by gas chromatography—negative ion chemical ionization—selected ion monitoring

A specific, sensitive and accurate quantitation method for glyceryl trinitrate was developed using gas chromatography—negative ion chemical ionization—selected ion monitoring with dichloromethane as a reagent gas. [¹⁵N₃] and [²H₅, ¹⁵N₃] variants were synthesized from non-labelled or [²H₈]glycerol and [¹⁵N]nitric acid. The former variant was used for preventing adsorption of glyceryl trinitrate onto active sites on column materials and the latter was used as an internal standard for quantitation of glyceryl trinitrate in biological fluids by selected ion monitoring. The quantitation limit of this method is 0.1 ng/ml of human plasma. When glyceryl trinitrate was administered intravenously in the dose of 4 μg/kg to patients receiving hypotensive anesthesia for surgical operation, the plasma levels exhibited a biexponential decay. The mean and standard deviation of half-lives of the α and β phases were found to be about 0.41 ± 0.13 and 5.34 ± 1.60 min, respectively.