Preparative chromatographic resolution of racemates using HPLC and SFC in a pharmaceutical discovery environment☆

Miller, Larry; Potter, Matt

doi:10.1016/j.jchromb.2008.06.044

Cited by 99 publications

(32 citation statements)

References 23 publications

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“…Enantioselective chromatography is a rapid means of accessing this information, and among chromatographic techniques, supercritical fluid chromatography (SFC) has proven to show high performances. [2][3][4] Indeed, the low viscosity of carbon dioxidebased mobile phases provides short analysis time together with high efficiency. For reviews on chiral separations by SFC, the reader is referred to the recent literature.…”

Section: Introductionmentioning

confidence: 99%

Chiral separation of phospine‐containing α‐amino acid derivatives using two complementary cellulosic stationary phases in supercritical fluid chromatography

et al. 2009

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Enantiomeric separations of six amino-acid derivatives have been studied using packed-column supercritical fluid chromatography with two polysaccharide-based enantioselective stationary phases: cellulose tris(3,5-dimethylphenylcarbamate) and cellulose tris(3-chloro-4-methylphenylcarbamate) (Lux Cellulose-1 and -2). The effect of analyte structure on retention and separation was studied. Varied mobile phase compositions were investigated: alcohol modifier percentage was increased from 3 to 40% but smaller amounts were most effective in separating these compounds. Besides, ethanol was preferred to methanol or isopropanol as it proved to be a good compromise to achieve sufficient resolution in a reasonable analysis time. Moreover, a carbon dioxide-ethanol mixture allows performing analyses in safe and green conditions. The effect of temperature at constant mobile phase composition was explored between 10 and 40 degrees C. In most cases, increasing the temperature improved the chiral separation, up to an optimum temperature. The results are discussed in line with the structure variation of the racemic derivatives analyzed and the two columns are compared. The two columns were shown to provide complementary selectivities for the investigated solutes: whereas Lux 1 provided separation for five of the six racemates, Lux 2 could resolve the last racemic mixture. Finally, optimized conditions of separation are defined.

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Section: Introductionmentioning

confidence: 99%

Chiral separation of phospine‐containing α‐amino acid derivatives using two complementary cellulosic stationary phases in supercritical fluid chromatography

et al. 2009

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“…Preparative SFC constituted an alternative choice in the context of implementation of techniques with reduced environmental impact [247]. It has been relatively well documented through various successful industrial scale-up processes and is expected to grow in the upcoming years [248][249][250]. Nevertheless, it should be kept in mind that the sharp decrease in solvent consumption must be weighted by the large amount of energy required to pressurize the CO 2 and to regulate the temperature along the chromatographic path [251].…”

Section: Advantages and Limitations Of Sfcmentioning

confidence: 99%

Evolution and Current Trends in Liquid and Supercritical Fluid Chromatography

Fekete¹,

Perrenoud²,

Guillarme

2014

CCHG

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Abstract:The current trend in high performance liquid chromatography (HPLC) tends toward the achievement of higher separation efficiency and shorter analysis time. Indeed, better performance in LC has become increasingly important in recent years mainly driven by the challenges of either analyzing more complex samples or increasing the numbers of samples per time unit. In the recent development of particle technology, the use of fully porous sub-2 m particles and sub-3 m shell particles have received considerable attention. Beside packed columns, the new generation of silica-based monolithic columns also offers very high separation power. However, to take full advantage of these innovative phases, the chromatographic system has also to be drastically optimized in terms of upper pressure limit and system volume.This revolution in column technology now spreads and covers several modes of liquid chromatography such as reversedphase liquid chromatography (RPLC), hydrophilic interaction liquid chromatography (HILIC), or even supercritical fluid chromatography (SFC). The HILIC and SFC, which can be considered as alternative modes of chromatography, could also be useful to extend the applicability of chromatography towards the analysis of very hydrophilic and lipophilic compounds, respectively.The present review gives an insight about the theory behind the success of current column technology and presents a summary of latest applications, using various modes of one-dimensional chromatography (RPLC, HILIC, SFC). This paper also shows that theoretically expected column efficiency could sometimes be compromised in practical work especially in the case of narrow bore columns.

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“…73,74 Fast and labor efficient racemic synthesis combined with preparative chiral chromatography can in many cases offer a strategic advantage over enantioselective synthesis approaches, especially in early development where compound attrition is very high. Figure 16 shows a typical example of the use of preparative chiral chromatography to resolve the enantiomers of an intermediate for the synthesis of a preclinical drug candidate.…”

Section: Mixture Of Stereoisomersmentioning

confidence: 99%

9.06 The Use of Preparative Chiral Chromatography for Accessing Enantiopurity in Pharmaceutical Discovery and Development

Welch

2014

Comprehensive Organic Synthesis II

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Preparative chromatographic resolution of racemates using HPLC and SFC in a pharmaceutical discovery environment☆

Cited by 99 publications

References 23 publications

Chiral separation of phospine‐containing α‐amino acid derivatives using two complementary cellulosic stationary phases in supercritical fluid chromatography

Chiral separation of phospine‐containing α‐amino acid derivatives using two complementary cellulosic stationary phases in supercritical fluid chromatography

Evolution and Current Trends in Liquid and Supercritical Fluid Chromatography

9.06 The Use of Preparative Chiral Chromatography for Accessing Enantiopurity in Pharmaceutical Discovery and Development

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