Quantification of eucalyptol (1,8-cineole) in rat serum by gas chromatography-mass/mass spectrometry and its application to a rat pharmacokinetic study.

Eucalyptol (1,8-cineole) is a biologically active cyclic monoterpenoid. In a preliminary study, we used gas chromatography-mass spectrometry to detect eucalyptol in the serum and brain tissue of rats after oral administration. However, the absorption characteristics in vivo and pharmacokinetic parameters of eucalyptol have not been published to date. The present study aims to develop and validate a simple, sensitive GC-MS/MS method with quadrupole mass analyzer type for the quantitative analysis of eucalyptol in rat serum and apply it to a pharmacokinetic study. The assay showed linearity of concentration range from 50 to 5,000 pg/ml with a limit of quantitation of 50 pg/ml. Intra- and inter-day precision for eucalyptol were 4.4-13.0 and <15.0%, respectively, and accuracy was within 10% for quality control samples. The recovery and stability results showed that the method was accurate and stable for quantitative analysis. The developed analytical method was successfully applied to a pharmacokinetic study after a single oral administration of eucalyptol in rat subjects. The serum concentration-time profiles indicate that the absorption characteristics of eucalyptol after oral administration are similar to those for intravenous administration.

Development of galangal essential oil-based microemulsion gel for transdermal delivery of flurbiprofen: simultaneous permeability evaluation of flurbiprofen and 1,8-cineole.

Flurbiprofen (FP) is one of the most potent nonsteroidal anti-inflammatory drugs with very low bioavailability of approximately 12% following transdermal administration, compared to that after oral administration. This study aimed to deliver FP as a microemulsion (ME) gel by transdermal administration. Galangal essential oil (GEO) was extracted from Rhizoma Alpiniae Officinarum and identified by GC-MS. The most abundant constituent was determined to be 1,8-cineole (52.06%). Compared to azone, GEO was proved to exert significantly higher (p < .01) penetration enhancement effect and significantly (p < .001) lower skin cell toxicity. The formulation (FP-GEO-ME gel) was prepared using GEO as an oil phase and a penetration enhancer. Compared to that of FP solution, the enhancement ratio (ER) of FP-GEO-ME gel was 4.06. In addition, more than 25% 1,8-cineole permeated through the rat skin. In vivo pharmacokinetic studies revealed that the AUC0-t of FP after transdermal administration of FP-GEO-ME gel was higher by approximately 4.56-fold than that of marketed FP cataplasms. The relative bioavailability of FP and 1,8-cineole after transdermal administration compared to oral administration of FP-GEO-ME were determined to be 96.58% and 85.49%, respectively. FP-GEO-ME gel significantly inhibited carrageenan-induced hind-paw edema and decreased PGE2 levels in rat serum. GEO-ME gel also exhibited significant anti-inflammatory effects at 2 h after the therapy (p < .05). The synergistic effects of FP and GEO were expected for the application of FP-GEO-ME gel. In conclusion, GEO-ME gel may be a promising formulation for transdermal administration of anti-inflammatory hydrophobic drugs, such as FP.