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Advisor(s)
Abstract(s)
Continuous preparative liquid chromatography is nowadays a well-established
technology used for the separation of a wide range of chemical mixtures. Among theseContinuous preparative liquid chromatography is nowadays a well-established
technology used for the separation of a wide range of chemical mixtures. Among these
techniques, the simulated moving bed (SMB) technology has gained an increasing
interest to the industry in the production of fine chemicals and pharmaceuticals. This
growing is due to the development of new and more versatile stationary phases, as
well as new operating schemes for SMB and other continuous chromatographic
processes.
In recent years, the authors have focused in the preparative separation of
chemical drugs by chiral SMB chromatography. Different case studies have been
considered, including the separation of non-steroidal anti-inflammatory drugs
(ketoprofen and flurbiprofen enantiomers) [1-4], and the pseudo-binary separation of
nadolol stereoisomers, a beta-blocker pharmaceutical drug [5]. While the first two case
studies are typical examples of binary chiral mixtures (a pair of enantiomers), the last
is an example of a quaternary mixture, composed by two pairs of enantiomers. This
considerably increases the complexity and the difficulty of the separation process,
asking for new strategies for the complete resolution of all the four components.
Experimental and simulation results have been recently presented considering
a first step of a pseudo-binary separation by SMB (the more retained component being
obtained pure in the extract and the other three co-eluting in the raffinate), followed by
a ternary separation through a JO process [6]. This work introduces a different strategy using an achiral C18 stationary phase under reversed-phase mode to perform a first
SMB separation step. The C18 achiral adsorbent allows the separation of the two pairs
of nadolol diastereomers, i.e., the first racemate (composed by the nadolol compounds
2 and 3) co-eluting in the raffinate, and the second racemate (composed by the nadolol
compounds 1 and 4) to be obtained in the extract SMB stream. After this preliminary
achiral separation step, two parallel SMB runs must be carried out using a chiral
stationary phase to achieve the complete separation of all the four nadolol
stereoisomers.
Description
Keywords
Continuous preparative liquid chromatography Simulated moving bed
Citation
Ribeiro, António E.; Arafah, Rami; Rodrigues, A.E.; Pais, L.S. (2014). Separation of nadolol stereoisomers by fixed-bed and continuous preparative liquid chromatography using C18 columns. In XVI Latin-American Congress on Chromatography & 9th National Meetoing on Chromatography. Lisbon
Publisher
FCUL