The Tibetan Medicine Standardization and New Drug R&D discipline group made a new breakthrough in the screening strategy of countercurrent chromatography solvent system

Counter-current chromatography (CCC) is a liquid-liquid chromatography technology, compared with the traditional liquid preparative chromatography technology, it has the advantages of no fixed phase death adsorption and 100% sample recovery, and is widely used
in separation science.
The selection of a solvent system based on the partition coefficient (K) is the most important step in CCC separation, and the optimization of solvent system selection accounts for up
to 90% of the workload in CCC separation.
At present, the selection and optimization of solvent system based on HPLC peak area trial and error method is the most commonly used method, which is time-consuming and labor-intensive, which limits the more in-depth and extensive application
of CCC in separation science.

Recently, the Tibetan Medicine Standardization and New Drug R&D Group of the Northwest Institute of Plateau Biology, Chinese Academy of Sciences, in collaboration with Qinghai Normal University and Jinan University, published a report entitled Ab initio calculation based solvent system selection in silico for counter-current in the Journal of Chromatography A (IF=4.
6).
Research paper
on chromatography: Separation of resibufogenin glycosylation product 。 This paper establishes a selection optimization strategy for ab initio calculation of CCC solvent system based on thermodynamic calculation and limiting optimization, which includes three steps: 1) the COSMO-RS model is used to calculate the partition coefficient of the given solvent system from scratch; 2) Using (non)linear fitting, establish a functional relationship between the ab initio calculation of the partition coefficient and the composition ratio of the given solvent system; 3) Using MATLAB, 0.
5 ≤ Ki ≤2.
5 and Ki/Kj≥1.
5 (Ki>Kj) are used as the boundary conditions, and minΣ (Ki) is used as the objective function for restriction optimization, so as to optimize and select a suitable solvent system
。 In order to verify the feasibility of the strategy in practical application, taking the glycosylation product of the ester toad toxicity ligand as the separation target, without any experimental operation data, the optimal solvent system was successfully optimized by this strategy, and the CCC separation and preparation of the target compound was well completed, and the optimized partition coefficient was calculated ab novo compared with the measured value of the posterior experiment
。 This strategy can almost 100% completely optimize the selection and optimization of CCC solvent system in the computer, without any experimental data, which greatly reduces the workload of solvent system selection optimization, improves the separation efficiency of CCC, and greatly promotes the wide and in-depth application
of CCC in conventional separation science.

Chen Tao, associate researcher of Northwest Plateau Institute, is the first author of this paper, Li Yulin, researcher of Northwest Plateau Institute, associate professor He Liangliang of Jinan University and associate professor Zou Denglang of Qinghai Normal University are co-corresponding authors
of the paper.
This work was supported by the National Natural Science Foundation of China (No.
32260129), Youth Promotion Association of Chinese Academy of Sciences (No.
2020425) and Qinghai Provincial Natural Science Foundation (No.
2021-ZJ-976Q).

Link to paper:

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