Development and validation of a simple and sensitive HPLC method for the determination of related substances in regorafenib tablets

Abstract

Regorafenib as an oral multi-kinase inhibitor has displayed a promising future in the anticancer drug market. However, there are no articles reporting the method for the determination of related substances in regorafenib tablets. A quality standard was first included in the Ph. Eur. 10.4 until April 2021 but could not detect seven known impurities A, C, D, E, FP-A, FP-B, and FP-C simultaneously. In this paper, a simple and sensitive HPLC method was established for the determination of related substances in regorafenib tablets. The determination was performed on a Polar-RP column with dual wavelength detection set at 230 nm and 260 nm. This method was validated according to the ICH guidelines. Furthermore, the possible sources of impurities were analyzed and forced degradation tests were performed, which provided guidance for formulation development and storage conditions. The established method is simple, sensitive and accurate for the determination of related substances in regorafenib tablets. Graphical abstract: A specified and sensitive HPLC method for the determination of related substances in regorafenib tablets[Figure not available: see fulltext.].