Quantitative analysis of atractylenolide I in rat plasma by LC-MS/MS method and its application to pharmacokinetic study

A new high-performance liquid chromatography/tandem mass spectrometry (LC-MS/MS) was developed for quantitative analysis of atractylenolide I in rat plasma using buspirone as internal standard (I.S.). Rat plasma samples were deproteined with methanol and acetonitrile (1:1, v/v). Atractylenolide I and I.S. were separated on a Phenomenex Gemini C-18 column (50 mm x 2.0 mm, 5 mu m) with gradient mobile phase at the flow rate of 0.4 ml/min. The detection was performed by positive ion electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode. The linear calibration curve of atractylenolide I in rat plasma ranged 2.0-5000 ng/ml (R > 0.9979). The limit of detection (LOD) and the limit of quantification (LOQ) were 0.6 ng/ml and 2.0 ng/ml, respectively. Both accuracy and precision of the assay were satisfactory. The recoveries of atractylenolide land I.S. were 91.4% and 87.8%, respectively. This fully validated method was applied to a pharmacokinetic study of atractylenolide I in rats administered with 20 g/kg Atractylodis extract. The main pharmacokinetic parameters T-max (the time to peak), C-max (the concentration to peak), T-0.5 (the biological half time), and K-e (the elimination rate constant) were 0.81 +/- 0.11 h, 7.99 +/- 1.2 ng/ml, 1.94 +/- 0.27 h, 0.365 +/- 0.06/h, respectively. (C) 2011 Elsevier B.V. All rights reserved.