Abstract

The present study sought to determine blood and plasma levels of 1,8-cineole in humans after inhalation and dermal application, respectively, over a period of 45 min. In addition, the influence of the inlet port liner, i.e., split or splitless, on quantification was evaluated. Eight young, healthy volunteers (4 males) took part in the study. In the inhalation condition, 1,8-cineole was delivered via a custom built inhalation apparatus. In the dermal application condition, the fragrance was massaged into the skin of the lower abdomen and odorless air was delivered via the inhalation apparatus. Blood was drawn from the right cubital vein at 5 min intervals starting 15 min until 45 min after the onset of fragrance administration. In addition, a blank sample was drawn at 0 min. All samples were quantified on a GC-MS system using (–)-linalool as the internal standard, static headspace (s-HS) injection and selected ion monitoring. Blood samples were incubated at two different temperatures before injection. Comparison of the s-HS calibration curves demonstrated that the split liner was superior to the splitless liner in terms of linearity. Regarding pharmacokinetics, the results showed that in either condition plasma levels of 1,8-cineole were somewhat higher than blood levels. In addition, both blood and plasma levels measured after inhalation were approximately ten times higher than those after dermal application. This finding was likely due to accumulation of 1,8-cineole in subcutaneous fatty tissue after penetration through the skin.

Keywords: 1, 8-Cineole, GC/MS, human whole blood, pharmacokinetics, port liner, static headspace.

Graphical Abstract