A mechanistic explanation on degradation behavior of flibanserin for identification and characterization of its potential degradants using LC-DAD/ESI/APCI-Q-TOF-MS/MS

Abstract

Sprout Pharmaceuticals got marketing approval for Flibanserin (FLB) from USFDA. It is a well-known fact that post-marketing research on impurity profiling significantly contributes to the improvement of quality, safety and efficacy of a drug. In this study, we performed a comprehensive forced degradation of FLB to identify and characterize its degradation impurities and establish the degradation pathways. All the potential degradation impurities were chromatographically separated and identified. Five new potential degradation products (DPs) were characterized using LC-DAD/ESI/APCI-Q-TOF-MS/MS. The plausible structure for all the DPs has been established employing their mass fragmentation pattern. Elemental compositions of the DPs were derived from accurate mass measurements and mass error in ppm. A probable mechanistic explanation has been established for formation of the DPs. Till date, no study has been reported on the degradation behavior of FLB before this. The degradation profiling of FLB reported in this study will provide a complete understanding of the entire possible degradation impurities of FLB. One or more identified degradation impurities can be recommended by the regulatory bodies as the marker for stability study of FLB. The analytical method we have developed can be used for routine quality control of this molecule to quantitate it in presence of their potential impurities. In continuation to this research, degradation kinetic study of FLB to establish the degradation behavior in different stress conditions, mass balance study to correlate the amount loss of parent drug with formation of DPs and evaluation of toxicity potential of the DPs are recommended to be conducted in future.