Stereochemical differentiation of C-7 hydroxyltaxane isomers by electrospray ionization mass spectrometry.
In this study, different electrospray ionization mass spectrometric (ESI-MS) methods were utilized to analyze several pairs of taxane stereoisomers including paclitaxel and 7-epi-paclitaxel. Both ESI-MS and tandem mass spectrometry (MS/MS) techniques provided stereochemically dependent mass spectra in negative-ion mode, and all studied stereoisomers could be easily distinguished based on their characteristic ions or distinct fragmentation patterns. MS/MS experiments for several taxane analogues at various collision energies were performed to elucidate potential dissociation pathways. The gas-phase deprotonation potentials were also calculated to estimate the most thermodynamically favorable deprotonation site using DFT B3LYP/6-31G(d). The results of the theoretical studies agreed well with the fragmentation patterns of paclitaxel and 7-epi-paclitaxel observed from MS/MS experiments. In addition, it was found that liquid chromatography (LC)/ESI-MS was a useful and sensitive technique for assignment of C-7 taxane stereoisomers from realistic samples.
Ge
Guang-Bo
GB
Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Zhang
Rong
R
Ai
Chun-Zhi
CZ
He
Yu-Qi
YQ
Zhang
Yan-Yan
YY
Liu
Xing-Bao
XB
Yang
Li
L
Wang
Zheng-Tao
ZT
Yang
Ling
L
D002853:Chromatography, Liquid / Q000379:methods; D008958:Models, Molecular; D015394:Molecular Structure; D017239:Paclitaxel / Q000737:chemistry; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013237:Stereoisomerism; D043823:Taxoids / Q000737:chemistry*
C111746:7-epipaclitaxel; D043823:Taxoids; D017239:Paclitaxel