Development of a Novel and Stability Indicating RP-HPLC-UV Method for Simultaneous Analysis of Carbetocin and Ten Impurities in Carbetocin Injection Products

A novel, simple and stability indicating reverse-phase high performance liquid chromatographic method with UV detection at 220 nm (RP-HPLC-UV) was established to realize the simultaneous analysis of carbetocin and ten related impurities. This paper performed the most comprehensive impurity profiling of carbetocin, including the synthesis-related impurities, the isomers of carbetocin and the degradants formed from the forced degradation research, the structures of which were tentatively identified by a two-dimensional liquid chromatography-mass spectrometry technology. The novelty of this RP-HPLC-UV method was demonstrated by its satisfactory resolution and selectivity, which was achieved using an YMC-pack C18 column kept at 40 ℃, and optimal organic modifier gradient. The mobile phase A was potassium dihydrogen phosphate buffer (pH 6.5)—acetonitrile (80:20, v/v), and the mobile phase B was potassium dihydrogen phosphate buffer (pH 6.5)—acetonitrile (72:28, v/v). The forced degradation research proved the stability-indicating capacity of the method and validation study was performed according to ICH requirements. In summary, this RP-HPLC-UV method could support the simultaneous determination of related substances of carbetocin in bulk drug and in pharmaceutical formulations.