US EPA

2240952 

Journal Article 

Plasma levels in man of nitroglycerin after buccal administration 

Bogaert, MG; Rosseel, MT 

1972 

Yes 

Journal of Pharmacy and Pharmacology
ISSN: 0022-3573 

NIOSH/00132110 

24 

9 

737-738 

English 

4404080 

A method was developed to measure plasma concentrations of nitroglycerin (55630) in humans after buccal administration. Gas chromatography with electron capture detection was used. The blood was centrifuged at 4 degrees-C and the plasma was removed and extracted 3 times with 5 milliliters of ethyl-acetate. The extracts were passed through a Norite filter, evaporated, and dissolved in 10 microliters of benzene. One to 2 microliters were injected into the gas chromatograph. Isosorbide-dinitrate was added to the plasma as an internal standard. Concentrations as low as 0.5 nanograms per milliliter of plasma were specifically measured. This method of analysis was tested on five volunteers who were given 600 to 2500 micrograms of nitroglycerin. After circulating the drug in their mouths for 3.5 minutes, spitting it out, and rinsing, venous blood samples were taken. The plasma concentrations of nitroglycerin were higher for the higher doses; 25 to 40 percent of the nitroglycerin was not absorbed. Some of the metabolites, such as 1,2-glyceryldinitrate (621658), and 1,3-glyceryldinitrate (623870) were detected in the saliva. The authors conclude that this method provides a sensitive method for the determination of nitroglycerin in plasma. These plasma concentrations of nitroglycerin after buccal administration can serve as reference values for future investigations.