A Sensitive LC-MS-MS Method for Quantification of 1,6-O,O-Diacetylbritannilactone in Rat Plasma and its Application in a Pharmacokinetic Study.

Abstract

1,6-O,O-Diacetylbritannilactone is a natural sesquiterpene lactone isolated from Inula britannica that has displayed cytotoxic effects against several human cancer cell lines. In this study, a selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed for determination of 1,6-O,O-diacetylbritannilactone in rat plasma. Chromatographic separation was achieved on an Agilent C18 column (4.6 mm × 75 mm, 3.5 μm) with methanol and water (80:20, v/v) as the mobile phase. An ESI source was applied and operated in positive ion mode; selected-reaction monitoring was used for quantification using target fragment ions m/z 373.2→312.9 for 1,6-O,O-diacetylbritannilactone and m/z 331.2→144.1 for the IS. Calibration plots were linear in the range of 1.5-1350 ng/mL for 1,6-O,O-diacetylbritannilactone in rat plasma. Intra- and inter-day precisions were <8.5%, and the accuracy ranged from -2.7 to 12.8%. The LC-MS-MS method was successfully applied in a pharmacokinetic study of 1,6-O,O-diacetylbritannilactone in rats.