Stereointegrity of thalidomide: gas-chromatographic determination of the enantiomerization barrier

Enantioselective chromatographic methods, representing the most commonly used techniques for the determination of enantiomeric ratios, can also be used for the evaluation of stereochemical integrity. In the present study, two chromatographic methods, dynamic gas chromatography (DGC) and stopped-flow...

Full description

Saved in:
Bibliographic Details
Published in:Journal of pharmaceutical and biomedical analysis 2002-01, Vol.27 (3), p.497-505
Main Authors: Trapp, Oliver, Schoetz, Gabriele, Schurig, Volker
Format: Article
Language:English
Subjects:
Chiral drug
Chromatography, Gas - methods
ChromWin
Dermatologic Agents - analysis
Dermatologic Agents - chemistry
Dynamic gas chromatography
Enantiomerization
Hypnotics and Sedatives - analysis
Hypnotics and Sedatives - chemistry
Stereoisomerism
Stop-flow gas chromatography
Thalidomide
Thalidomide - analysis
Thalidomide - chemistry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Enantioselective chromatographic methods, representing the most commonly used techniques for the determination of enantiomeric ratios, can also be used for the evaluation of stereochemical integrity. In the present study, two chromatographic methods, dynamic gas chromatography (DGC) and stopped-flow gas chromatography (SFGC) were used to determine the enantiomerization barrier of thalidomide. In the presence of a chiral stationary phase (CSP), the enantiomers of thalidomide produced characteristic elution profiles exhibiting plateaus and/or peak broadening which were observed between 190 and 220 °C in DGC. To obtain the enantiomerization barrier of thalidomide from experimental data, the fast and efficient simulation program ChromWin was used to simulate the elution profiles and obtain kinetic activation parameters. From temperature-dependent measurements the rate constants k 1 and k −1 and the kinetic activation parameters Δ G # , Δ H # and Δ S # of the enantiomerization of thalidomide were obtained by DGC. The enantiomerization barrier Δ G # was determined to be 154±2 kJ/mol with DGC and 150±3 kJ/mol with the sfGC technique at 200 °C, respectively. The concept of the retention increment R′ has been applied to separate the enantiomerization barrier of thalidomide in the dissolved and complexed state of the CSP.
ISSN:0731-7085
1873-264X
DOI:10.1016/S0731-7085(01)00573-8