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Low-temperature nanofiltration concentration process for DAC eluent preparation

Dynamic Axial Compression Column (DAC) is an advanced preparative chromatography technique. By continuously applying pressure through a hydraulic system during the compound chromatographic separation process, it can prevent the column bed from collapsing, maintain high column efficiency, and possess excellent reproducibility and the characteristic of linear scalability. It is widely used in the preparation and separation of high-purity compounds in industries such as pharmaceuticals, fine chemicals, and food processing. 

When preparing products with enhanced purity using DAC technology, the resulting products usually have similar structures and physical and chemical properties to the main component, but with poor separation, low yield, numerous analogues, high purity requirements for the main component, and unstable properties of the main component product. 

The preparation of DAC relies on chromatographic packing materials and mobile phases for the precise separation of compounds. Common DAC packing materials include normal phase silica gel, reversed phase silica gel, hybrid silica gel, HILIC silica gel, etc. Normal phase silica gel uses anhydrous or low-water organic solvents as the mobile phase; reversed phase silica gel and HILIC silica gel usually use methanol-water and acetonitrile-water as the mobile phase. 

Prepared by DAC, although high-purity compound sample solutions can be obtained, to obtain high-purity solid samples from the eluent prepared by DAC, usually several processing steps such as concentration → desalination and deacidification → freeze-drying or crystallization filtration drying are required. The preparation of high-purity solids from the DAC eluent is often also a technical challenge. 

The DAC elution solution contains methanol or acetonitrile, a high proportion of water; it also contains trifluoroacetic acid, acetic acid, and ammonium acetate. The concentrated solution is prepared through vacuum concentration, which is efficient and cost-effective but is prone to causing product degradation, thereby erasing the advantages of high-purity DAC preparation. In the industry, the nanofiltration concentration method is commonly used to concentrate low-concentration aqueous solutions. 

However, the DAC elution solution contains a high concentration of acetonitrile, which is extremely likely to cause swelling, dissolution and damage to the ordinary nanofiltration membrane, or a decline in its retention performance; the trifluoroacetic acid contained in the DAC elution solution is acidic with a pH below 2, and the ordinary nanofiltration membrane cannot withstand it for a long time. 

To solve the problem of nanofiltration concentration of the DAC elution solution, Wuhan Bona, through membrane application process research, has developed a direct nanofiltration concentration process for the DAC preparation elution solution containing acetonitrile, achieving: 

● Low-temperature concentration at 5 to 20 degrees Celsius 

High concentration, with a solid content of up to 10-20% 

● Resistant to methanol 

● Resistant to acetonitrile 

Resistant to trifluoroacetic acid 

● High desalination rate (sodium acetate, ammonium acetate, sodium formate, ammonium formate, etc.) 

● High retention rate 

The low-temperature nanofiltration concentration process for preparing elution solution using DAC has been applied to products such as high-value-added peptide intermediates, ADC and PDC small molecule drugs, and tetracycline intermediate drugs. This process has effectively improved production efficiency and product quality, and possesses significant process advantages.