title: Direct Separation of Pregabalin Enantiomers Using a Zwitterionic Chiral Selector by High Performance Liquid Chromatography Coupled to Mass Spectrometry and Ultraviolet Detection.
abstract: The chromatographic resolution of pregabalin enantiomers has been often achieved by derivatization of the molecule, in order to reach enough sensitivity at low concentrations of the minor enantiomer present in the active principle. In the present article, the development and optimization of two liquid chromatographic methods are presented for the direct resolution of pregabalin enantiomers on a chiral stationary phase (CSP) containing a zwitterionic selector derived from cinchona alkaloid and sulfonic acid (CHIRALPAK ZWIX). The key parameters for the separation as well as the compatibility of chromatographic conditions with different detection modes (ultraviolet and mass spectrometry) were investigated. The resulting methods were found to be selective, of high performance and low limits of detection (2 µg/mL by UV and 1 ng/mL by MS, respectively) and quantification (6 µg/mL by UV and 5 ng/mL by MS, respectively) for the minor enantiomer which is considered as a chiral impurity.
authors.affiliation: Daicel Chiral Technologies India, Pvt Ltd, Lab n° 4A, IKP Knowledge Park, Shameerpet, Hyderabad 500078, India. lakshminarayana@chiral.daicel.com.
authors.forename: Lakshmi Narayana
authors.initials: LN
authors.lastname: Chennuru
authors.affiliation: Daicel Chiral Technologies India, Pvt Ltd, Lab n° 4A, IKP Knowledge Park, Shameerpet, Hyderabad 500078, India. thirupathi@chiral.daicel.com.
authors.forename: Thirupathi
authors.initials: T
authors.lastname: Choppari
authors.affiliation: Daicel Chiral Technologies India, Pvt Ltd, Lab n° 4A, IKP Knowledge Park, Shameerpet, Hyderabad 500078, India. ramakrishna@chiral.daicel.com.
authors.forename: Ramakrishna Prasad
authors.initials: RP
authors.lastname: Nandula
authors.affiliation: Chiral Technologies Europe, Parc d'Innovation, Bd. Gonthier d'Andernach, Illkirch F‑67400, France. tzhang@chiral.fr.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Chiral Technologies Europe, Parc d'Innovation, Bd. Gonthier d'Andernach, Illkirch F‑67400, France. pfranco@chiral.fr.
authors.forename: Pilar
authors.initials: P
authors.lastname: Franco
mesh_terms: D002851:Chromatography, High Pressure Liquid; D013058:Mass Spectrometry; D015394:Molecular Structure; D056951:Photoelectron Spectroscopy; D000069583:Pregabalin / Q000737:chemistry* / Q000302:isolation & purification*
chemical_list: D000069583:Pregabalin
keywords: chiral stationary phases; direct enantiomer separation by HPLC; mass spectrometry; method optimization; pregabalin; ultraviolet detection; zwitterionic selector