Multicomponent separation of nadolol stereoisomers combining different preparative technologies and chiral and achiral-chiral strategies
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abstract
Nadolol is a common prescribed pharmaceutical drug for the relieve of several cardiovascular diseases and represents a very interesting case-study of multicomponent chiral separation since it is composed by four stereoisomers, being two pairs of enantiomers. In this way, it introduces the possibility of alternative strategies, using different kind of preparative separation sequences and techniques, the use of different packings (chiral and achiral stationary phases), and the corresponding mobile phase optimization at both normal and reversed-phase modes.
When considering preparative and multicomponent separation, the complexity deeply increases by introducing the necessity of multi-step separation sequences (or a much more complex multi-region separation process), by opening the possibility to combine chiral and achiral stationary phases (when in presence of stereoisomers instead of just one pair of enantiomers) and to combine different separation techniques (fixed-bed and simulated moving bed (SMB) related processes). The design of the complete preparative separation of nadolol stereoisomers asks for a global experimental and simulation methodology considering both the characterization and optimization of each separation step and its sequences to achieve the four nadolol components pure. New strategies using combinations of achiral and chiral stationary phases and sequences of different separation techniques will be presented. Extensive experimental and simulation results for the complete separation of all the four nadolol stereoisomers using Chiralpak IA (chiral) and different Waters C18 (achiral) stationary phases will be presented.
This work is a result of project “AIProcMat@N2020-Advanced Industrial Processes and Materials for a Sustainable Northern Region of Portugal 2020,” with the reference NORTE‐01‐0145‐FEDER‐000006, supported by Norte Portugal Regional Operational Program (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and of project POCI‐01‐0145‐FEDER‐006984-Associate Laboratory LSRE‐LCM funded by ERDF through COMPETE2020-Programa Operacional Competitividade e Internacionalização (POCI)—and by national funds through Fundação para a Ciência e a Tecnologia (FCT)
