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 μg/mL (r2 = 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.

A new validated high‐performance liquid chromatography method for the determination of regorafenib in rat plasma: Application for pharmacokinetic study

“…Although these values are similar to previously published pharmacokinetic parameters of REG, the low Cmax value points out that sampling times are correct and could be determined with high sensitivity. Among the reported methods, only two were performed using an HPLC‐PDA‐UV device and only one was performed in rat plasma [7, 8]. Our method is 10 times more sensitive than the reported method, and the analysis time is considerably shorter.…”

“…To date, there is no record of Regorafenib's active ingredient determination in pharmacopeias. Existing literature includes only two high-performance liquid chromatography-ultraviolet (HPLC-UV) detection methods, one of which is applicable to rat plasma [7,8]. One study focused on the simultaneous detection of REG and its major metabolites in plasma using solid-phase extraction for protein precipitation and extraction.…”