1. Sensitivity improvement of circular dichroism detection in HPLC by using a low-pass electronic noise filter: Application to the enantiomeric determination purity of a basic drug
- Author
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Jean-Paul Ribet, Marie Lorin, Philippe Morin, Raphaël Delépée, Jean-Claude Maurizot, Institut de Chimie Organique et Analytique (ICOA), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Orléans (UO)-Institut de Chimie du CNRS (INC), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), and PIERRE FABRE-PIERRE FABRE
- Subjects
Circular dichroism ,enantiomeric purity ,Resolution (mass spectrometry) ,Calibration curve ,Analytical chemistry ,2-adrenoreceptor antagonist ,010501 environmental sciences ,Sensitivity and Specificity ,01 natural sciences ,High-performance liquid chromatography ,Concentration ratio ,Catalysis ,Analytical Chemistry ,Drug Discovery ,Adrenergic alpha-Antagonists ,Chromatography, High Pressure Liquid ,Spectroscopy ,Benzofurans ,0105 earth and related environmental sciences ,Pharmacology ,Detection limit ,low-pass electronic noise filter ,Chromatography ,quantitation ,Chemistry ,010401 analytical chemistry ,Organic Chemistry ,Imidazoles ,Stereoisomerism ,Repeatability ,0104 chemical sciences ,circular dichroism ,efaroxan ,Enantiomer ,HPLC ,polysaccharide stationary phase - Abstract
The quality control of chiral drugs requires the determination of their enantiomeric purity. Nowadays, circular dichroism (CD) spectroscopy is gaining increasing importance in pharmaceutical analysis because of the commercially available CD detector in liquid chromatography. The separation of the two enantiomers of a basic drug (efaroxan) was achieved by high performance liquid chromatography using an amylose-derivated column with both UV and CD detections. A baseline-resolved separation (resolution: 5) was obtained after optimization of the mobile phase composition with hexane-ethanol-diethylamine (90:10:0.05; v/v/v). The use of a commercial low-pass electronic noise filter of the CD signal has improved the signal-to-noise ratio by a factor twelve and allowed the quantitation of each enantiomer in the 1.25-300 microg ml(-1) concentration range. The CD linear calibration curve, expressed in terms of stereoisomer height ratio versus concentration ratio, was plotted over the 0.4-6% range. A correlation coefficient greater than 0.999 was obtained by least-squares regression and the limit of detection for the distomer/eutomer ratio was estimated at 0.14%. Although the method validation showed good repeatability on the retention times (RSD0.9%), on the peak height ratios (RSD8.7%) of each enantiomer only up to 99.2% enantiomeric purity was achieved.
- Published
- 2007
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