A reverse phase HPLC method for the separation of two stereo isomers of 2‐[4‐(methylsulfonyl)phenyl]‐3‐(3(r)‐oxocyclopentyl)propanoic acid

Abstract

This study describes successful method development and separation of two stereo isomers of 2-[4-(methylsulfonyl)phenyl]-3-(3(R)-oxocyclopentyl)propanoic acid by reverse phase high-performance liquid chromatography. Baseline resolution was achieved on a J'sphere-ODS-H80 (150 mm × 4.6 mm, 4 μm) column using mobile phase consisting of 0.05% triflouroacetic acid in water-acetonitrile (85:15, v/v) at a flow rate of 1.0 ml/min. The detection was carried out at 228 nm. The title compound, in turn, can be obtained by C-alkylation of methyl 2-[4-(methylthio)phenyl]acetate with 2(S)-iodomethyl-8,8-dimethyl-6,10-dioxaspiro[4.5]decane followed by consecutive hydrolysis and oxidation. The partially validated analytical method (system suitability, peak homogeneity, linearity, precision, robustness, and solution stability) has limit of detection and limit of quantification, 0.15 and 0.50 μg/ml respectively. Alternatively, the new method is being routinely utilized to monitor epimerization of α-carbon of the propanoic acid in the title compound by crystallization-induced dynamic resolution.