A sensitive liquid chromatography–tandem mass spectrometry method for pharmacokinetics and tissue distribution of nuciferine in rats

Nuciferine is an important drug candidate for the treatment of obesity-related diseases. However, few investigations have been conducted about the pharmacokinetics and tissue distribution of nuciferine to better understand its behavior and action mechanism in vivo. Thus, a sensitive and reliable liquid chromatography with tandem mass spectrometry (HPLC–MS/MS) method was established and validated for the quantification of nuciferine in rat plasma and tissue samples. The validated method was successfully applied to the pharmacokinetic and tissue distribution study of nuciferine in rats. One-compartmental pharmacokinetic parameters indicated that nuciferine had rapid distribution, extensive tissue uptake, and poor absorption into systemic circulation. The values of absolute bioavailability were (3.8 ± 1.4)%, (4.2 ± 1.3)% and (3.9 ± 1.0)% after oral administration of 2.0, 5.0 and 10.0 mg/kg nuciferine and intravenous administration of 0.2 mg/kg nuciferine in rats. The results of the tissue distribution study suggested that nuciferine was distributed into the brain, liver and adipose tissue after intravenous administration. In conclusion, the present study may provide a material basis for study of the pharmacological action of nuciferine in the treatment of obesity, and meaningful insights into further study on dosage modification.