Determination of enantiomeric purity of S‐amlodipine by chiral LC with emphasis on reversal of enantiomer elution order |
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Authors: | Katina S. S. Dossou Patrick A. Edorh Patrice Chiap Bezhan Chankvetadze Anne‐Catherine Servais Marianne Fillet Jacques Crommen |
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Affiliation: | 1. Laboratory of Analytical Pharmaceutical Chemistry, Department of Pharmaceutical Sciences, CIRM, University of Liege, Liege, Belgium;2. Laboratory of Environmental Toxicology, Departement of Biochimistry and Cellular Biology, University of Abomey‐Calavi, Cotonou, Benin;3. Advanced Technology Corporation (A.T.C.), University Hospital of Liege, Liege, Belgium;4. Institute of Physical and Analytical Chemistry, School of Exact and Natural Sciences, Tbilisi State University, Tbilisi, Georgia |
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Abstract: | An LC method was developed and prevalidated for the enantiomeric purity determination of S‐amlodipine in polar organic solvent chromatography using a chlorine‐containing cellulose‐based chiral stationary phase (CSP). The concentration of formic acid (FA) (0.01–0.2%) in the mobile phase containing acetonitrile as the main solvent was found to influence the elution order of amlodipine enantiomers as well as the enantioresolution. A reversal of the enantiomer elution order of amlodipine was only observed with chiral stationary phases with both electron‐withdrawing (chloro) and electron‐donating groups (methyl) on the phenyl moieties of the chiral selector, namely cellulose tris(3‐chloro‐4‐methylphenylcarbamate) and cellulose tris(4‐chloro‐3‐methylphenylcarbamate). The highest enantioresolution (Rs: 4.1) value was obtained at the lowest FA concentration (0.01%) using cellulose tris(4‐chloro‐3‐methylphenylcarbamate) as the chiral selector and the enantiomeric impurity, R‐amlodipine, eluted first under these conditions. Therefore, the mobile phase selected for the prevalidation of the method consisted of ACN/0.1% DEA/0.01% FA and the temperature was set at 25°C. The method was prevalidated by means of the strategy based on the total measurement error and the accuracy profile. The method was found to be selective and the limit of quantification was found to be about 0.05% for R‐amlodipine, while the limit of detection was close to 0.02%. |
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Keywords: | Acidic additive Chlorinated cellulose‐based chiral stationary phases Prevalidation Reversal of enantiomer elution order S‐Amlodipine enantiomeric purity |
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