Development and validation of a sensitive liquid chromatography/tandem mass spectrometry method for the determination of raddeanin A in rat plasma and its application to a pharmacokinetic study

A simple and sensitive high-performance liquid chromatography–electro-spray ionization tandem mass spectrometry (LC–ESI-MS/MS) method was developed and validated to determine raddeanin A in rat plasma. After precipitation of rat plasma samples with methanol, chromatographic separation was achieved on a BDS Hypersil C18 column (100 × 2.1 mm, 2.4 μm) using the mobile phase consisted of acetonitrile and 2 mM ammonium acetate with 0.05% formic acid (60:40, v/v). The detection was performed in a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode using negative ionization. The transition monitored were m/z 895.6 → 455.0 for raddeanin A and m/z 359.3 → 329.0 for IS, respectively. The method was linear over the concentration range of 2–1000 ng/mL for raddeanin A. The intra-day and inter-day assay variations were <9.46%, and the accuracy values were between −2.04% and −6.52% relative error. The extraction recovery of raddeanin A was more than 70%, and the relative matrix effect ranges from 108.52% to 112.36%. The validated method has been successfully applied to determine the pharmacokinetic profile of raddeanin A in rat plasma following oral and intravenous administration.

► A sensitive method for analysis of raddeanin A in rat plasma is proposed.
► Method combined protein precipitation and LC–MS/MS.
► The pharmacokinetic study of raddeanin A in rats is firstly reported.
► The method offers a lower LOQ for raddeanin A than conventional methods.