Separation of the Two Enantiomers of Naproxcinod by Chiral Normal-Phase Liquid Chromatography

A normal-phase enantioselective high-performance liquid chromatographic method was developed for the enantiomeric resolution of naproxcinod, the most advanced cyclooxygenaseinhibiting nitric oxide donator of anti-inflammatory drugs designed for treatment of osteoarthritis. The enantiomers of naproxcinod were resolved on a Chiralpak AD-H (250 × 4.6 mm, 5 µm) column using a mobile phase system containing n-hexane and 2-propanol (95:5, v/v). The resolution between the enantiomers was found to be more than 2.0. The limit of detection and limit of quantitation of (R)-enantiomer were found to be 5 and 15 ng/mL, respectively, for 20 µL injection volume. The sample solution and mobile phase were found to be stable for at least 48 h. The final optimized method was successfully applied to separate (R)-enantiomer from naproxcinod and was proven to be reproducible and accurate for the quantitative determination of (R)-enantiomer in bulk drugs.