Synthesis and evaluation of a novel chiral derivatization reagent for resolution of carboxylic acid enantiomers by RP-HPLC

Publication date: Available online 14 September 2017 Source:Microchemical Journal Author(s): Lu-Ping Li, Mei-Na Jin, Qing Shi, Chun-Yan Xu, Ying-Zi Jiang, Yong-Ill Lee, Jun Zhe Min A novel derivatization reagent, N-[1-Oxo-5-(triphenylphosphonium)pentyl]-(S)-3-aminopyrrolidine (OTPA), with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge was developed for the enantiomeric separation of chiral carboxylic acids by high-performance liquid chromatography (HPLC). OTPA reacted with the carboxylic acids at 40°C within 90min in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and 1-hydroxybenzotriazole (HOBt). The degree of epimerization (racemization) during the derivatization reaction was negligible. The separability of the diastereomers was evaluated in terms of their resolution value (Rs). The Rs values of the derivatives of non-steroidal anti-inflammatory drugs (NSAIDs), which were selected as the representative carboxylic acids, were completely separated by reversed-phase chromatography using an ODS (4.6mm×150mm I.D., 5.0μm) column. The resolution Rs values were 1.54–2.23 for the evaluated carboxylic acids and the OTPA-derivatization was also effective for the enantiomeric separation of chiral carboxylic acids. The calibration curves (r2 >0.9971) were linear over the concentration range of 0.0125–1.25mM for each enantiomer of ketoprofen (KET), and naproxen (NAP), 0.05–1.0mM for each enantiomer of ibup...
Source: Microchemical Journal - Category: Chemistry Source Type: research