Determination of xanthatin by ultra high performance liquid chromatography coupled with triple quadrupole mass spectrometry: Application to pharmacokinetic study of xanthatin in rat plasma

• Xanthatin possesses a variety of biological activities.
• A UHPLC–MS/MS method was established to determine the concentration of xanthatin in rats plasma.
• The pharmacokinetic properties of xanthatin in rats plasma were investigated for the first time.

A sensitive, specific and rapid ultra high performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) method has been established to study pharmacokinetic properties of xanthatin. Xanthatin, a compound which belongs to sesquiterpene lactone group, was determined in rat plasma with psoralen as internal standard. Chromatographic separation was performed on an Agilent Zorbax Eclipse plus C18 column (50 mm × 2.1 mm, 3.5 μm) with gradient elution system at a flow rate of 0.3 mL/min. The mobile phase was composed of methanol and 0.1% formic acid water solution. Analysis was performed under a triple-quadruple tandem mass-spectrometer with an electrospray ionization (ESI) source via the multiple reaction monitoring (MRM) mode to determine xanthatin at [M+H]+m/z 247.3 → m/z 205.2 and that of IS at [M+H]+m/z 187.1 → m/z 143.0 within 5 min. The assay method exhibited good separation of xanthatin from the interference of endogenous substances. The lower limit of quantification (LLOQ) was 1 ng/mL, with a good linearity within the concentration range of 1–5000 ng/mL (r = 0.9990). Intra-day and inter-day precision RSD was less than 9.27%; intra-day and inter-day accuracy was 88.48% and 102.25% respectively. The extraction recoveries of xanthatin range from 82.12% to 89.55%, and the extraction RSD was less than 9.01%. The established LC–ESI-MS/MS method is rapid and sensitive, which has been successfully applied to quantify xanthatin in rat plasma for the first time.