Analysis of isobutyl nitrite inhalant in rat and human blood: application for pharmacokinetic investigations.

Organic nitrites have been used therapeutically for the treatment of angina pectoris and as diagnostic agents for the evaluation of cardiac heart murmurs. In addition, these highly volatile vasodilators are being used as inhalant drugs of abuse. We developed a gas chromatographic assay using electron capture detection for the analysis of a representative nitrite inhalant, isobutyl nitrite (ISBN), in rat and human whole blood. Unconventional sampling and processing techniques were required because of the high volatility and chemical instability of nitrites in biological fluids. Our method produced a mean recovery of ISBN from rat blood of about 86% over a concentration range of 1.0 to 400 ng/ml. The inter-day coefficient of variation was below 15% at the lowest quantifiable concentration of 1 ng/ml ISBN in rat blood. In this report, we applied the analytical method to obtain new pharmacokinetic information about ISBN. Results show that rats inhaling 900 ppm ISBN for 45 min produced steady-state blood concentrations of about 290 ng/ml, and a rapid elimination half-life of 1.4 min.