Determination of d-limonene in mice plasma and tissues by a new GC-MS/MS method: Comparison of the pharmacokinetics and tissue distribution by oral and inhalation administration in mice

The aim of the present study was to develop a method based on gas chromatography-tandem mass spectrometry (GC-MS/MS) to determine and quantify the d-limonene in mouse plasma and tissue samples. This new method was validated for the quantification of d-limonene with the linearity ranges 1.0-1000.0 ng/mL (r(2) > 0.9952) for plasma samples and 5.0-5000.0 ng/g (r(2) > 0.9940) for tissue samples. The intra- and inter-day assay of precisions in plasma and tissues were <13.4% and the accuracies were within 91.1-105.8%. In the oral/inhalation administration pharmacokinetics and tissue distribution studies, the main pharmacokinetic parameters were the peak concentration = (97.150 +/- 34.450)/(4336.415 +/- 1142.418) ng/mL, the area under the curve = (162.828 +/- 27.447)/(2085.721 +/- 547.787) h ng/mL and the half-life = (3.196 +/- 0.825)/(0.989 +/- 0.095) h. The tissue distribution of d-limonene in mice after oral/inhalation administration demonstrated a decreasing tendency in different tissues (liver > kidney > heart > lung > spleen).