Determination of enantiomeric composition of ibuprofen in pharmaceutical formulations by partial least-squares regression of strongly overlapped chromatographic profiles

In this report, we demonstrate how chiral liquid chromatography combined with multivariate chemometric techniques, specifically unfolded-partial least-squares regression (U-PLS), provides a powerful analytical methodology. Using U-PLS, strongly overlapped enantiomer profiles in a sample could be successfully processed and enantiomeric purity could be accurately determined without requiring baseline enantioresolution between peaks. The samples were partially enantioseparated with a permethyl-β-cyclodextrin chiral column under reversed-phase conditions. Signals detected with a diode-array detector within a wavelength range from 198 to 241 nm were recorded, and the data were processed by a second-order multivariate algorithm to decrease detection limits. The R-(−)-enantiomer of ibuprofen in tablet formulation samples could be determined at the level of 0.5 mg L−1 in the presence of 99.9% of the S-(+)-enantiomorph with relative prediction error within ±3%.

► Chemometric methods and chromatographic–spectroscopic data were applied. ► Partial least-squares regression was used to analyze overlapped enantiomer signals. ► Enantiomeric purity can be accurately determined without baseline enantioresolution. ► The R-(−)-ibuprofen was measured in the presence of 99.9% of the S-enantiomorph.