Determination of artemisitene in rat plasma by ultra‐performance liquid chromatography/tandem mass spectrometry and its application in pharmacokinetics

Rationale Artemisitene shows a wide variety of pharmacological activities, such as antioxidant protection in vitro and in vivo . It has been identified as a novel Nrf2 inducer. However, there is no report on an ultra‐performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method to quantitate artemisitene in rat plasma and its application to a pharmacokinetic profile study. Methods An ACQUITY UPLC™ BEH Symmetry Shield RP18 column (1.7 μm, 2.1 mm × 100 mm) was used at a flow rate of 0.3 mL·min –1 . Mass detection was performed by electrospray ionization tandem mass spectrometry via multiple reaction monitoring (MRM) in positive mode. Plasma samples were pre‐treated by a single‐step extraction with 0.1% formic acid aqueous solutions‐acetonitrile, and tolbutamide was used as internal standard. Results The calibration curve was from 0.98 to 1000 ng∙mL –1 (r 2 = 0.995). The extraction recoveries were 61.5–79.4% and 81.7–94.6% for artemisitene and tolbutamide, respectively. The lower limit of quantification (LLOQ) was 0.98 ng∙mL –1 . The absolute bioavailability of artemisitene was 3.7% after intravenous and oral administration in rats. Conclusions The UPLC/MS/MS assay was validated for linearity, accuracy, stability, extraction recovery, matrix effects, and intra‐day and inter‐day precision. The method, for the first time, achieved some pharmacokinetic parameters and was successfully applied to a pharmacokinetic study Copyright © 2017 John Wiley & Sons, Ltd.