Determination of parthenolide in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study

• UPLC-MS/MS assay for parthenolide determination in rat plasma.
• The method offered shorter run time of 3.0 min.
• The method is accurate, precise and meets validation requirements by guideline.

A rapid, sensitive and selective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the determination and pharmacokinetic investigation of parthenolide in rat plasma. Sample preparation was accomplished through a simple one-step deproteinization procedure with 0.2 mL of acetonitrile containing 30 ng/mL of pirfenidone (IS), and to a 0.1 mL plasma sample. Plasma samples were separated by UPLC on an Acquity UPLC BEH C18 column using a mobile phase consisting of acetonitrile-0.1% formic acid in water with gradient elution. The total run time was 3.0 min and the elution of parthenolide was at 1.33 min. The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction-monitoring (MRM) mode using the respective transitions m/z 249.2 → 231.1 for parthenolide and m/z 186.2 → 92.1 for pirfenidone (IS), respectively. The calibration curve was linear over the range of 2.0–500 ng/mL with a lower limit of quantitation (LLOQ) of 2.0 ng/mL. Mean recovery of parthenolide in plasma was in the range of 78.2–86.6%. Intra-day and inter-day precision were both <8.3%. This method was successfully applied in pharmacokinetic study after oral and intravenous administration of parthenolide in rats.

Figure optionsDownload as PowerPoint slide