Electrospray-ionization mass spectrometry study of cyclodextrin complexes with A007 prodrugs

被引:1
|
作者
SagiRaju, Sarada [1 ]
Chen, Kan [1 ]
Cole, Richard B. [1 ]
Jursic, Branko S. [1 ]
机构
[1] Univ New Orleans, Dept Chem, New Orleans, LA 70148 USA
关键词
Electrospray; Cyclodextrin; Inclusion complexes; A007; prodrugs; Molecular associates; ESIMS; ALPHA-CYCLODEXTRIN; CYTOCHROME-P-450; ENZYMES; OXIDATION; CHEMICALS;
D O I
10.1016/j.carres.2009.06.042
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Electrospray-ionization mass spectrometric (ESIMS) studies of several A007 prodrugs in aqueous cyclomaltohexaose (alpha-cyclodextrin, alpha-CD), cyclomaltoheptaose (beta-cyclodextrin, beta-Cl), and cyclomaltooctaose (gamma-cyclodextrin, gamma-CD) were performed. The acetic acid derivative of A007 should metabolize in vivo before becoming the A007 prodrug, while on the other hand, the glycine-modified A007 prodrug has surfactant-like physical properties and slowly hydrolyzed in the aqueous cyclodextrins by releasing free A007. ESIMS studies give insight into the process of prodrug hydrolysis in the presence of cyclodextrins and, hence, the influence of cyclodextrins on the timely release of the A007 prodrug. Formation of various molecular aggregates and cyclodextrin inclusion complexes of A007 prodrugs and their hydrolyzed products was demonstrated by ESIMS. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2167 / 2172
页数:6
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