Enantiodifferentiation of promethazine using (S)-(−)-BINOL as the NMR chiral solvating agent: determination of the enantiomeric purity and performance comparison with traditional chiral HPLC

The enantiomeric excess of optically active promethazine was determined for the first time by a proton nuclear magnetic resonance (1H NMR) spectroscopic enantiodifferentiation method by means of (S)-(−)-1,1′-bi(2-naphthol) [(S)-(−)-BINOL] as a chiral solvating agent (CSA), and additionally ascertained by HPLC measurements on Chiralcel® OJ chiral column. The results obtained for the enantiopurity of standard samples of promethazine were almost fully consistent with those established by chiral HPLC (quantitative to approximately 1% minor enantiomer). The developed method is simple, rapid, inexpensive, repeatable, sensitive, and very selective toward promethazine enantiomers, and may serve for its routine quantitative analysis.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide