UPLC–MS/MS performing pharmacokinetic and biodistribution studies of rhein

Abstract

Rhein, an important constituent of Radix et Rhizoma Rhei, has been used to alleviate liver and kidney damage. In this work, plasma pharmacokinetic and biodistribution characteristics of rhein after oral administration was investigated using a rapid and sensitive ultra‐performance liquid chromatography coupled to tandem high‐definition mass spectrometry (UPLC–MS/MS) method. Mass spectrometry was performed on a Waters Micromass high‐definition technology with an electrospray ionization source in positive ion mode. Biosamples were prepared using methanolic precipitation and the separation of rhein was achieved on a UPLC HSS T3 column by linear gradient elution and the total run time was only 4.70 min. Data were analyzed and estimated by compartmental methods using WinNonlin Professional version 5.1. Mean pharmacokinetic parameters following single‐dose administration of rhein was consistent with a two‐compartmental open model. It was found that rhein was distributed and eliminated rapidly in rats and the biodistribution showed the higher levels were in liver, spleen, kidney, heart, lung and the lower level observed in the muscle, adrenal, and thyroid. It was not discovered in brain and showed that rhein could not cross the blood–brain barrier. Our developed UPLC–MS/MS approach was capable of providing complete pharmacokinetic and biodistribution parameters for rhein when administered orally.