Comparison of cyclodextrin-barbiturate noncovalent complexes using electrospray ionization mass spectrometry and capillary electrophoresis

Abstract

Various noncovalent complexes between native and derivatized cyclodextrins (CDs) and barbiturates were studied using capillary electrophoresis (CE) and electrospray ionization mass spectrometry (ESI-MS). This paper involves the study of four aspects of CD-barbiturate noncovalent inclusion complexes. The first study focused on determining the formation of CD-barbiturate inclusion complexes in ESI-MS. This determination was accomplished by the comparison of migration data from CE with ESI-MS inclusion complex peak abundances, which were found to be complementary. The second study found the possibility of predicting native beta-CD mediated CE elution orders for barbiturates using data from ESI-MS. A third study focused on the formation of barbiturate inclusion complexes with derivatized beta-CD and gamma-CD. As part of this study, the effect of the extent of side chain substitution on native CD complexation behavior was investigated. The results indicated that the number of side chains on the CD does not affect the formation of barbiturate complexes with the hydrophobic CD cavity. Finally, a comparison of the hydroxypropyl-beta-CD-barbiturate and hydroxypropyl-gamma-CD-barbiturate complexes in CE and ESI-MS was made to study the relationship between strength of drug-CD binding and enantioresolution. The results from the above studies indicated that the gas phase and the solution state complexes showed comparable behavior indicating that similar interactions played a role in stabilizing these complexes. While it was possible to use the ESI-MS data to determine drug binding to the CDs, it was not possible to predict whether a separation of the enantiomers of a chiral barbiturate would occur. However, the ESI-MS data could be used to eliminate certain CDs from consideration as chiral selectors.

Comparison of local anesthetic-cyclodextrin non-covalent complexes using capillary electrophoresis and electrospray ionization mass spectrometry

“…Previously, the formation of true host-guest inclusion com- plexes with ␤-CD had been reported [3,25]. As observed in this study, the presence of an additional heterocyclic moiety in the anesthetic structure enhances the binding with the ␤-CD.…”

“…A previous study performed in this lab showed the formation of specific non-covalent complexes of a group of acidic hypnotic agents [3]. In this study, we extend this approach to a group of basic local anesthetics in an attempt to determine whether the behavior previously observed was limited to the acidic compounds or is more universal in its applicability.…”

“…The electric current increases by decreasing the solvent conductivity, which causes the analyte to move faster in the sample plug until encountering the boundary of the higher concentration buffer [3,14]. This approach causes the analyte to be stacked in a narrow zone producing sharper peaks.…”

“…The gas phase environment of the mass spectrometer has the advantage of avoiding many interferences and allows for facile identification and detection of host-guest complexes [2]. Numerous studies have reported the observation of intact non-covalent complexes and this information was used to provide insight into specific non-covalent associations in solution [1][2][3][4][5][6]. However, the production of non-specific adducts have been reported too, leading to concerns over the ability of mass spectrometry to be used to study non-covalent associations [7,8].…”

Determination of 13 Organic Toxicants in Human Blood by Liquid-Liquid Extraction Coupling High-Performance Liquid Chromatography Tandem Mass Spectrometry

“…The OMT, DMT, DDVP, CBF, FEN DZP, EST, ALP, TAL, CLP and PNG were sensitive in PI mode, whereas the analysis of the BBT and PNB was carried out in NI mode because they were not possible to be optimized in the PI mode according literatures. 46,47 In order to select precursor ions for each analyte, chromatograms were recorded in the full scan mode. In this work, protonated molecular ions for DMT, OMT, DDVP, CBF, Table 2.…”