Chiral Separation of Three Anti-Inflammatory Drugs by Liquid Chromatography on Polysaccharide-Type Stationary Phases and Pirkle-Type Phase

Abstract

In this work, the enantioseparation of three anti-inflammatory drugs (naproxen, ibuprofen, and thalidomide) was investigated on seven different polysaccharide-type stationary phases (ReproSil Chiral-MIG, ReproSil Chiral-MID, ReproSil Chiral-AM, ReproSil Chiral-JM, ReproSil Chiral-MIC, Lux i-Amylose-1, and Lux Amylose-2) and a Pirkle-type phase (ReproSil Chiral-NR) using Normal (NP) and Reverse (RP) phase systems. Along with the separation capacity of the applied systems, our study focuses on the resolution, the effect of mobile phase mixtures, retention times, selectivity, and the number of theoretical plates. The studies enabled the determination of optimal chromatographic conditions that provide the best separation results for the individual enantiomers of anti-inflammatory drugs. Thalidomide separated best on a ReproSil Chiral-MIG amylose column in a system of 99% acetonitrile and 1% water (v/v) with a resolution (R_s) of 9.410. Naproxen separated best on a column with a Pirkle-type phase in the same solvent system, 95 : 5 (v/v), with a resolution (R_s) of 1.186. Ibuprofen did not separate on columns with a Pirkle-type phase or cellulose packing. Partial separation was achieved on the ReproSil Chiral-MID amylose column in a system of 85% n-heptane and 15% 1-propanol (v/v), yielding a resolution (R_s) of 1.169. These studies enabled the verification of the separation of three drugs, for which only one of the enantiomers typically has a therapeutic effect. This finding is valuable from the perspective of human health. Our studies focus on a wide range of polysaccharide stationary phases, a brush column, and as many as ten solvent systems; furthermore, the elution order was determined wherever possible. Several variables enabled the drawing of both general and specific conclusions, considering the structure of the analytes and the column packings.