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Supercritical fluid chromatography and steady‐state recycling: Phase appropriate technologies for the resolutions of pharmaceutical intermediates in the early drug development stage
Author(s) -
Yan Tony Q.,
Orihuela Carlos,
Preston Jay P.,
Xia Fang
Publication year - 2010
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20861
Subject(s) - supercritical fluid chromatography , chemistry , supercritical fluid , chromatography , solubility , high performance liquid chromatography , solvent , impurity , diastereomer , stationary phase , phase (matter) , organic chemistry
The use of phase appropriate technologies is critical for efficiently moving drug candidates forward in the early stages of drug discovery and development. Phase appropriate purification technology develops the analytical method and subsequently scales up the method and turns the sample around quickly (Kennedy et al., J Chromatogr A 2004; 1046:55). In this article, separation results and conditions from supercritical fluid chromatography (SFC), high‐performance liquid chromatography (HPLC), and steady‐state recycling (SSR) for the resolutions of three pharmaceutical intermediates in the early stage of the drug development are discussed. The first study used SFC and SSR to separate an impurity for a Good Manufacturing Practice (GMP) campaign. The analytical method development and scale‐up conditions are discussed. Productivity, solvent usage, and sample solubility under SFC and SSR conditions are also compared. The second study compared SFC to batch HPLC in separating a diastereomer. Due to higher separation efficiency, SFC was able to resolute multiple peaks. The third study involved the addition of dichloromethane as a co‐solvent in SFC purification—improving sample selectivity and solubility. From the separation results of these purifications, SFC and SSR are clearly phase appropriate technologies in the early drug development stage. Chirality, 2010. © 2010 Wiley‐Liss, Inc.