The pharmacokinetics and tissue distribution of coumaroylspinosin in rat: A novel flavone C-glycoside derived from Zizyphi Spinosi Semen

Zizyphi Spinosi Semen (ZSS) has a long history of sedative-hypnotic use in China. As a novel flavone C-glycoside, coumaroylspinosin is a main flavonoid only found in ZSS. Up to now, its pharmacokinetic information and tissue distribution in vivo are not available yet. With a simple, rapid and sensitive HPLC-MS/MS method, the pharmacokinetics and tissue distribution of coumaroylspinosin were investigated in Sprague-Dawley (SD) rats after its intravenous administration. Puerarin was used as the internal standard (IS). The samples were extracted by a simple protein precipitation method with methanol. The MS analysis was performed with multiple reaction monitoring (MRM), and the transitions were set at m/z 753.3 → 427.0 for coumaroylspinosin and m/z 415.3 → 295.3 for IS, respectively. The method was successfully applied for investigating the pharmacokinetics and tissue distribution of coumaroylspinosin in Sprague Dawley (SD) rats after tail vein injection with 4.0 mg/kg of the flavonoid. The calibration curves covered over the range of 0.02-10 μg/mL in plasma and various tissues samples with good linearity(r ≥ 0.9956). The lower limit of quantification (LLOQ) in all samples was less than 20 ng/mL. The intra- and inter-day precisions were below 15% and accuracy was from −3.78% to 4.68%. No significant matrix effect was observed, and the average extraction recovery was acceptable. Coumaroylspinosin could be cleared quickly from the rat plasma with the half-life (t1/2) of 1.86 ± 0.15 h. It was distribute widely in vivo, and the main tissue depots of coumaroylspinosin in rats were found to be intestine, muscle and lung. With the method, the pharmacokinetic parameters and tissue distribution of coumaroylspinosin in SD rats were investigated for the first time. The results demonstrated that coumaroylspinosin was distributed widely and rapidly in various rat tissues after intravenous administration.