Premium
Determination of the Enantiomeric Purity of the Antiasthmatic Drug Montelukast by Means of 1 H NMR Spectroscopy
Author(s) -
Redondo Jordi,
Capdevila Anna,
Ciudad Sonia
Publication year - 2013
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.22213
Subject(s) - chemistry , enantiomer , diastereomer , enantioselective synthesis , cinchonidine , proton nmr , chirality (physics) , nuclear magnetic resonance spectroscopy , chromatography , capillary electrophoresis , stereochemistry , organic chemistry , combinatorial chemistry , catalysis , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark
In order to define an enantioselective nuclear magnetic resonance (NMR) method for the antiasthmatic drug montelukast, a series of nine easily available products were evaluated as NMR chiral solvating agents (CSAs): D‐dibenzoyltartaric acid, D‐ditoluoyltartaric acid, (+)‐camphorsulfonic acid, ( S )‐BINOL, ( S )‐3,3’‐diphenyl‐2,2’‐binaphthyl‐1,1’‐diol, ( R )‐3,3'′‐di‐9‐anthracenyl‐1,1'′‐bi‐2‐naphthol, ( R )‐3,3'′‐di‐9‐phenanthrenyl‐1,1'′‐bi‐2‐naphthol, Pirkle's alcohol, and (−)‐cinchonidine. It was proved that most of the studied agents constitute diastereomeric complexes with both drug enantiomers in CD 2 Cl 2 or CDCl 3 solutions, thus permitting the direct 1 H NMR detection of the unwanted S ‐enantiomer, even at levels of 0.75%. (−)‐Cinchonidine was found to be the more convenient CSA in terms of NMR enantiodiscrimination power and ease of experimental requirements. The final method was validated and applied to the fast monitoring of the optical purity of montelukast “in‐process” samples, circumventing the need for tedious and slower analytical procedures like enantioselective chromatography or capillary electrophoresis . In addition, a method for the enantiopurity control of the commercial drug (montelukast sodium salt) was also established using ( S )‐BINOL as NMR CSA. Chirality 25: 780–786, 2013 . © 2013 Wiley Periodicals, Inc.