HPLC-MS/MS-Mediated Analysis of the Pharmacokinetics, Bioavailability, and Tissue Distribution of Schisandrol B in Rats

Abstract

Schisandrol B, a lignan isolated from dried Schisandra chinensis fruits, has been shown to exhibit hepatoprotective, cardioprotective, renoprotective, and memory-enhancing properties. This study sought to design a sensitive and efficient HPLC-MS/MS approach to measuring Schisandrol B levels in rat plasma and tissues in order to assess the pharmacokinetics, oral bioavailability, and tissue distributions of this compound in vivo. For this analysis, bifendate was chosen as an internal standard (IS). A liquid-liquid extraction (LLE) approach was employed for the preparation of samples that were subsequently separated with an Agilent ZORBAX Eclipse XDB-C₁₈ (4.6 × 150 mm, 5 μm) column with an isocratic mobile phase consisting of methanol and water containing 5 mM ammonium acetate and 0.1% formic acid (90 : 10, v/v). A linear calibration curve was obtained over the 5-2000 ng/mL and 1-1000 ng/mL ranges for plasma samples and tissue homogenates, respectively. This established method was then successfully applied to investigate the pharmacokinetics, oral bioavailability, and tissue distributions of Schisandrol B in Sprague-Dawley (SD) rats that were intravenously administered 2 mg/kg of Schisandrol B monomer, intragastrically administered Schisandrol B monomer (10 mg/kg), or intragastrically administered 6 mL/kg SCE (equivalent to 15 mg/kg Schisandrol B monomer). The oral absolute bioavailability of Schisandrol B following intragastric Schisandrol B monomer and SCE administration was approximately 18.73% and 68.12%, respectively. Tissue distribution studies revealed that Schisandrol B was distributed throughout several tested tissues, with particular accumulation in the liver and kidneys. Our data represent a valuable foundation for future studies of the pharmacologic and biological characteristics of Schisandrol B.

Figure 1

Representative multiple reaction monitoring chromatograms of Schisandrol B (a) and the internal standard bifendate (b).

Figure 2

Typical chromatograms of Schisandrol B and IS in blank rat plasma (a) and liver homogenates (b); blank rat plasma (c) and liver homogenates (d) spiked with LLOQ and IS; and rat plasma (e) at 1 h and liver homogenate samples at 0.5 h (f) following the oral administration of 10 mg/kg Schisandrol B. A corresponds to Schisandrol B, and B corresponds to IS.

Figure 3

Mean plasma concentration-time curves for Schisandrol B following the intravenous administration of 2 mg/kg of monomer (a), the intragastric administration of 10 mg/kg monomer (b), and the intragastric administration of 6 mL/kg SCE (equivalent to 15 mg/kg of Schisandrol B monomer) (c).

Figure 4

The concentration-time profile of Schisandrol B in tissues following oral administration (n = 3).