Pharmacokinetics and tissue distribution of Aucubin, Ajugol and Catalpol in rats using a validated simultaneous LC–ESI-MS/MS assay

• The determination of Aucubin, Ajugol and Catalpol in rat plasma and tissue by LC–MS/MS.
• The LLOQ for three analytes is 1 ng/mL in all biological fluids.
• The method was used to a preclinical pharmacokinetics and tissue distribution study.
• Higher level of Aucubin, Ajugol and Catalpol were found in kidney tissue.
• Aucubin and Catalpol could cross the blood–brain barrier.

To enable an investigation of pharmacokinetics and tissue distribution of Aucubin, Ajugol and Catalpol in rats, a high-performance liquid chromatography–electro spray ionization tandem mass spectrometry (HPLC–ESI–MS/MS) method was developed for the simultaneous quantitative determination of the three compounds. Biological samples were prepared by a simple protein precipitation with methanol (containing 0.05% formic acid). The analytes were separated by a C18 reversed phase column and detected with a triple quadrupole tandem mass spectrometer in the multiple-reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 364.3 → 149.0 for Aucubin, m/z 366.5 → 151.1 for Ajugol, m/z 380.0 → 183.3 for Catalpol and m/z 530.3 → 183.1 for Picroside-II (IS) in positive ionization. Good linearity of each calibration curve was produced over the concentration range of 1–1000 ng/mL. The lower limit of quantification (LLOQ) was 1 ng/mL for the three analytes. This method was successfully applied to the pharmacokinetic and tissue distribution studies of Aucubin, Ajugol and Catalpol in rat. The current results revealed pharmacokinetic behaviors of the herb compound and provided novel evidence of the presence of Aucubin and Catalpol in rat brain. The acquired data would be helpful for the clinical application and further studies of Traditional Chinese Medicines (TCM) with active ingredients of Iridoid Glycosides.