Pharmacokinetics and tissue distribution study of schisandrin B in rats by ultra-fast liquid chromatography with tandem mass spectrometry

The concentration–time profile of schisandrin B in tissues after oral administration at a dose of 4mg/kg to rats (n=6). [Display omitted] ► Development of an UFLC–MS/MS method to determine schisandrin B in biological matrix. ► Pharmacokinetic curve of schisandrin B showed double peaks in rat plasma. ► Schisandrin B was mainly accumulated in liver in rats. ► Renal excretion might be a main elimination route for schisandrin B in rats. A rapid, sensitive and high throughput ultra-fast liquid chromatography with tandem mass spectrometry (UFLC–MS/MS) method was established and validated for the determination of schisandrin B in rat plasma and various tissues (including heart, liver, spleen, lung, and kidney). The biological samples were prepared by protein precipitation, and the separation was achieved on a shim-pack XR-ODS C18 column (75mm×3.0mm, 2.2μm) with a mobile phase consisting of methanol–0.1% formic acid water (85:15, v/v) at a flow rate of 0.4mL/min. The MS/MS detection was performed on an API 3200 QTRAP mass spectrometry equipped with electrospray ionization (ESI) source using multiple reactions monitoring (MRM) mode by monitoring the fragmentation of m/z 401.2→300.2 for schisandrin B and m/z 271.2→203.1 for imperatorin (internal standard, IS). The calibration curve was linear in the range of 1–500ng/mL for plasma and tissue homogenates (r≥0.9927). The lower limit of quantification (LLOQ) was 1ng/mL. The validated method was successfully applied to the pharmacokinetics and tissue distribution study of schisandrin B after oral administration to rats. The pharmacokinetic curve showed double peaks after oral administration, which demonstrated that a hepatoenteral circulation may exist. Tissue distribution showed the highest level was observed in liver, then in kidney, which indicated schisandrin B was mainly accumulated in liver and renal excretion might be a main elimination route.