Development of a Simple, Precise, and Validated HPLC Method for the Anticancer Drug, Regorafenib: Application to Pharmacokinetics in Rats and Stability Study

Abstract

The goal of this study was to establish a simple, precise, and validated high-performance liquid chromatography-ultraviolet (HPLC-UV) method to quantify the amount of regorafenib in rat plasma using revaprazan as an internal standard. The mobile phase composition was 0.1% aqueous trifluoroacetic acid solution and 0.1% trifluoroacetic acid in acetonitrile (50/50, v/v). The flow rate was 0.5 mL/min, and the eluent was monitored at 265 nm. The results showed that this novel chromatographic method achieved the criteria of the FDA validation guidelines and presented excellent linearity over 0.0488-50 mu g/mL (r(2) = 0.9999) concentration. Additionally, this method was validated for evaluating regorafenib stability in three different storage conditions and was effectively utilized to analyze the drug concentration in rat plasma after oral administration by calculating its pharmacokinetic parameters. Therefore, this HPLC method is appropriate for evaluating the pharmacokinetics of regorafenib in rats.