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

Chiral separations of R,S-naproxen mixtures were obtained on an achiral col umn (ODS) with methyl-p-cyclodextrin as a mobile phase additive using conve ntional and nano-LC. The optimised mobile phase composition was 20 mmol l(- 1) methyl-beta -cyclodextrin, 20% (v/v) acetonitrile, and 50 mmol l(-1) sod ium acetate buffer at pH 3 using hydrochloric acid for pH adjustment. In ad dition to UV detection at 232 nm, amperometric detection was also investiga ted. Without using any internal standard, the reproducibility of amperometr ic detection ( +1.05 V vs. Ag/AgCl) over a long analysis cycle in LC was gr eatly improved by choosing the peak area ratio between R- and S-naproxen as the analytical readout (the relative standard deviation was 2.11%) and ena ntiomeric purity could be assessed directly. This method was successfully e mployed 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. (C) 2001 Publ ished by Elsevier Science B.V.