Simultaneous and dynamic measurement of Schisandrol A changes in rat blood and brain and its comparative pharmacokinetic study in control and Parkinson's disease rats by dual-probe in vivo microdialysis.

Schisandrol A (SchA) is the main active ingredient of Schisandra chinensis (Turcz.) Baill., which is a famous traditional Chinese herbal medicine. SchA can penetrate the blood-brain barrier and has a significant neuroprotective effect. A group of multiplexed stable isotope mass tags (MSIMTs, m/z 332, 338, 346, 349, 351, 354, 360, 363, 374 and 377) were synthesized to perform multiplexed stable isotope labeling derivatization (MSILD) of SchA in rat microdialysates and standards. A new magnetic molecularly imprinted polymer was prepared using MSIMT-375-SchA as dummy template. All the 10-plexed derivatives of MSIMTs-SchA can be efficiently and selectively enriched and purified using this adsorbent by magnetic dispersive solid phase extraction (MDSPE) before ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) analysis. It should be pointed out that the MSIMT-346-SchA standard derivative was used as internal standard in the process of MDSPE and UHPLC-MS/MS. On these bases, 9 different rat microdialysate samples can be determined by UHPLC-MS/MS in a single run. The utilization of MSIMTs significantly increased the sensitivity, accuracy, selectivity and analysis throughput. Under the optimized conditions, satisfactory linearity (R2> 0.987), limit of detection (LODs, 0.15-0.26 pg/mL) and lower limit of quantitative (LLOQ, 0.8-2.0 pg/mL) were obtained. Intra- and inter-day precisions were in the range of 2.2% -12.5%, and recoveries 94.2% -106.2%. The matrix effects were very low, and the average derivatization efficiency of 10-plex MSIMTs to SchA was as high as 97.8%. Using the developed dual-probe in vivo microdialysis sampling technique, the proposed analytical method has been applied for comparative pharmacokinetics of SchA in the brain and blood of control and Parkinson's disease (PD) rats.