Vinorelbine-related Impurities Study

Vinorelbine Bitartrate,developed by Pierre Fabre ,is a unique semi-synthetic vinca alkaloid antitumor.Some relative impurities created during raw material preparation sample production and storage.It is compulsory to take some measure to control or eliminate these impurities.A method of high-performance liquid chromatography coupled with electrospray ionization mass spectrometry was developed to separate and identify sample relative impurities or degradation impurities.The analytical HPLC was carried out on a VP-ODS column (150*4.6mm)using 0.05M ammonium formicate buffer (PH4.2) and methanol(47:53) as mobile phase at a flow rate of 1.5ml/min temperature 35℃ and wavelength 267nm.The on-line mass spectrometry was performed using ion trap analyzer with ESI source. The result indicated the LC-MS method was simply and good repetition.Four unknown impurities were collected and identified by NMR.The four unknown impurities were respectively 21'-O-demthylvinorelbine 23-O-demthylvinorelbine 6'-N-mthyl vinorelbine 17-bromovinorelbine.The sample impress factor testing was performed under light heat humidity acidity alkaline oxidation reduction. The sample was very unsteady during light experiment and the mainly impurities were photodegradation and 23-O-demthylvinorelbine. The sample was unsteady during heat experiment and the mainly impurities were 21'-O-demthylvinorelbine 6 '-N-mthylvinorelbine. The only degradation product under the acidity or alkaline condition was speculated as 4-O-deacetylvinorelbine.All this data offered the theory basis of control the production and store condition of the sample.