Enantiomeric separation of R,S-naproxen by conventional and nano-liquid chromatography with methyl-β-cyclodextrin as a mobile phase additive

Chiral separations of R,S-naproxen mixtures were obtained on an achiral column (ODS) with methyl-β-cyclodextrin as a mobile phase additive using conventional and nano-LC. The optimised mobile phase composition was 20 mmol l−1 methyl-β-cyclodextrin, 20% (v/v) acetonitrile, and 50 mmol l−1 sodium acetate buffer at pH 3 using hydrochloric acid for pH adjustment. In addition to UV detection at 232 nm, amperometric detection was also investigated. Without using any internal standard, the reproducibility of amperometric detection (+1.05 V vs. Ag/AgCl) over a long analysis cycle in LC was greatly improved by choosing the peak area ratio between R- and S-naproxen as the analytical readout (the relative standard deviation was 2.11%) and enantiomeric purity could be assessed directly. This method was successfully employed for enantiomeric purity assessment in commercial naproxen tablets. Finally, successful transfer from conventional LC to nano-LC was realised, resulting in over 1000-fold reduction in reagent consumption.