Characterization of impurities in semi-synthetic vinorelbine bitartrate by HPLC-MS with mass spectrometric shift technique.
A simple and sensitive method of high-performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC/ESI-MS) was developed to separate and identify impurities in semi-synthetic vinorelbine bitartrate sample. The analytical HPLC was carried out on a reversed-phase C8 column using 0.02 M ammonium formicate buffer (pH 4.2) and methanol (46:54, v/v) as mobile phase at a flow rate of 0.8 ml/min at room temperature and a UV detection at 267 nm. The on-line HPLC/ESI-MS/MS was performed using ion trap analyzer in positive ion mode. Applying mass spectrometric shift technique to HPLC/ESI-MS/MS analysis, four impurities were identified as 18'-O-demethylvinorelbine (impurity-1), 6'-N-methylvinorelbine (impurity-2), 23-O-demethylvinoreline (impurity-3) and 17-bromovinorelbine (impurity-4), respectively, in investigated vinorelbine bitartrate sample. The four impurities, in which the impurity-1 was not reported as the semi-synthetic process impurity for vinorelbine bitartrate elsewhere, were isolated by preparative high-performance liquid chromatography. Their structures were further confirmed by means of 1D and 2D NMR spectra. Structural elucidation by spectral data was discussed.
Cao
Xiaoji
X
Department of Chemistry, Zhejiang University, Zhejiang Province, Hangzhou, China.
Tai
Yuanpo
Y
Sun
Cuirong
C
Wang
Kuiwu
K
Pan
Yuanjiang
Y
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015394:Molecular Structure; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000737:chemistry; D000077235:Vinorelbine
D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D000077235:Vinorelbine