Automated countercurrent chromatography method development and process scale-up at GlaxoSmithKline

Thornton, David J.; Yang, Xinglun; Hsu, Leo

doi:10.1016/j.chroma.2017.01.037

Cited by 7 publications

(3 citation statements)

References 14 publications

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“…Preparative HSCCC shares similarities with HPLC in that the flow rate can be scaled up based on cross-sectional area or volume ratios [26]. Consequently, we assessed the impact of flow rate augmentation on enantiomeric separation under different scenarios, while balancing critical factors such as stationary phase retention, resolution, and separation time (refer to Table 3).…”

Section: Predicting Separation Conditions For Preparative Hsccc After...mentioning

confidence: 99%

Continuous chiral separation process for high‐speed countercurrent chromatography established and scaled up: A case of Voriconazole enantioseparation

Sun,

Huang,

Pei

et al. 2024

J of Separation Science

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An efficient method for the continuous separation of Voriconazole enantiomers was developed using sulfobutyl ether‐β‐cyclodextrin (SBE‐β‐CD) as a chiral selector in high‐speed countercurrent chromatography (HSCCC) with different types. The separation was performed using a two‐phase solvent system consisting of n‐hexane/ethyl acetate/100 mmol/L phosphate buffer solution (pH = 3.0, containing 50 mmol/L SBE‐β‐CD) (1.5:0.5:2, v/v/v). A fast and predictable scale‐up process was achieved using an analytical DE HSCCC instrument. The optimized parameters were subsequently applied to a preparative Tauto HSCCC instrument, resulting in consistent separation time and enantiomeric purity, with throughput boosted by a remarkable 11‐fold. Preparative HSCCC successfully separated 506 mg of the racemate, delivering enantiomers exceeding 99% purity as confirmed by high‐performance liquid chromatography analysis. This investigation presents an effective methodology for forecasting the HSCCC scale‐up process and attaining continuous separation of chiral drugs.

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Section: Predicting Separation Conditions For Preparative Hsccc After...mentioning

confidence: 99%

Continuous chiral separation process for high‐speed countercurrent chromatography established and scaled up: A case of Voriconazole enantioseparation

Sun,

Huang,

Pei

et al. 2024

J of Separation Science

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show abstract

“…Taking advantage of the liquid nature of the stationary phase, unique operations can be performed, such as elution‐extrusion, back‐extrusion, dual‐mode, and the reversal of the mobile phase and the stationary phase . In addition, it is easy to scale up to high‐capacity scale based on K values and frequently has maximum sample recovery . What's more, it had been proved to be a good choice to purify flavone dimers .…”

Section: Introductionmentioning

confidence: 99%

Preparative separation of flavone dimers from Dysosma versipellis by counter‐current chromatography: Trifluoroacetic acid as a solvent system modifier

Yang

Guo

Han

2018

J of Separation Science

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The separation of natural products is grueling and time-consuming work with repeated isolations needed to obtain purified compounds. However, using counter-current chromatography, a unique liquid-liquid partition chromatography, constituents can usually be purified efficiently. During the separation of flavone dimers from Dysosma versipellis (Hance) by counter-current chromatography, the separation resolution and sample loading was impeded by the emulsification of the sample. By screening, trifluoroacetic acid was selected as the solvent modifier to eliminate the emulsification. Then, a quaternary solvent system of hexane/ethyl acetate/methanol/water (4:6:5:5 v/v/v/v) with trifluoroacetic acid at a low concentration of 0.5% v/v was used to purify the components from D. versipellis. Compared to that without trifluoroacetic acid, the separation resolution as well as the sample loading both increased greatly. In addition, flavone dimers in low concentrations could be enriched and purified at high sample loading. As a result, five podophyllotoxins and 11 flavonoids were purified and characterized by interpretation of spectroscopic data, in which two of eight flavone dimers were new and a known flavone dimer was first separated from this species.

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“…Taking advantage of the liquid nature of the stationary phase, unique operations can be performed, such as elution‐extrusion, back‐extrusion, dual‐mode and the reversal of the mobile phase and the stationary phase . In addition, it is easy to scale‐up to high‐capacity scale based on K values . Therefore, we decided to try CCC fractionation of the hydro‐distillation of essential oils of Cinnamomum camphora (L.) Presl.…”

Section: Introductionmentioning

confidence: 99%

Gram‐scale separation of borneol and camphor fromCinnamomum camphora(L.) Presl by continuous counter‐current chromatography

Yang

Guo

Han

et al. 2018

Separation Science Plus

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Borneol and camphor are well known bicyclic monoterpenoids and have been widely used in food, senior aromatic spices and folk medicine in China, India and Japan for more than 2000 years. Although they can be obtained by recrystallization or sublimation, it is still a challenge to prepare high‐purity borneol and camphor with high yields. In this study, we introduce a new continuous counter‐current chromatography method for the gram‐scale preparation of borneol and camphor from Cinnamomum camphora (L.) Presl using heptane/ethyl acetate/methanol/water quaternary solvent system and heptane/methanol/water ternary solvent system. Compared to the heptane/ethyl acetate/methanol/water solvent system, the heptane/methanol/water solvent system was found to possess higher loading capacity, and the heptane/methanol/water (10:7:3, v/v/v) solvent system was found to be the optimal solvent system for the separation of the distillation products of C. camphora. As a result, borneol and camphor were well obtained in a one‐step separation with a purity of over 99.9%. In addition, continuous injections method using “on demand” solvent system formulation was used to improve the separation efficiency and reduce solvent consumption, whose results indicated that counter‐current chromatography was a powerful and efficient tool to obtain borneol and camphor with high purity.

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Automated countercurrent chromatography method development and process scale-up at GlaxoSmithKline

Cited by 7 publications

References 14 publications

Continuous chiral separation process for high‐speed countercurrent chromatography established and scaled up: A case of Voriconazole enantioseparation

Continuous chiral separation process for high‐speed countercurrent chromatography established and scaled up: A case of Voriconazole enantioseparation

Preparative separation of flavone dimers from Dysosma versipellis by counter‐current chromatography: Trifluoroacetic acid as a solvent system modifier

Gram‐scale separation of borneol and camphor fromCinnamomum camphora(L.) Presl by continuous counter‐current chromatography

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