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A molecular model to explain paclitaxel and docetaxel sensitivity changes through adduct formation with primary amines in electrospray ionization mass spectrometry
Author(s) -
Iyer Sunil S.,
Gao Songmei,
Zhang ZongPing,
Kellogg Glen E.,
Karnes H. Thomas
Publication year - 2005
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.1914
Subject(s) - chemistry , adduct , docetaxel , mass spectrometry , electrospray ionization , paclitaxel , electrospray , molecular model , chromatography , amine gas treating , analyte , analytical chemistry (journal) , organic chemistry , cancer , medicine
The objective of this study was to adopt a molecular modeling approach to understand changes in signal intensity due to adduct formation with short‐chain alkylamines for two anticancer agents, paclitaxel and docetaxel, during electrospray mass spectrometric analysis. We describe a simple and intuitive modeling procedure using a comparison of hydropathic interaction (HINT) scores to explain differences in responses of amine adducts formed with the two analytes. The responses of paclitaxel and docetaxel were generally enhanced considerably (up to ∼500% in some instances) on adding the amines. However, for the docetaxel adduct formed with added decylamine in the mobile phase, the response dropped by 32%. A mechanistic understanding for this behavior is proposed, and binding scores calculated from corresponding molecular models were found to be consistent with the trend obtained from mass spectrometric data. Copyright © 2005 John Wiley & Sons, Ltd.