Capillary electrochromatography method for splitting pantoprazole racemate
By coating phenylazole tetracarboxylic acid-BD-CH3-L-cysteine as a chiral selective agent on a capillary electrochromatography column, the problem of pantoprazole racemate resolution was solved, and efficient resolution and simplification were achieved Preparation provides technical support for single enantiomer drug research.
Patent Information
- Application Number
- CN202411672205.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-21
- Publication Date
- 2025-01-07
AI Technical Summary
The existing technology is difficult to effectively disassemble the racemates of pantoprazole, which leads to challenges in the research and development of single enantiomer drugs, especially the low separation efficiency of left-hand and dextrome, which affects the therapeutic effect of the drug.
Using chiral open-tube capillary electrochromatography column, it is physically coated onto the inner wall of the capillary through phenylatic acid-BD-CH3-L-cysteine as a chiral selector, and Pantopra is achieved through capillary electrochromatography. Enantiomer resolution of azole.
The efficient separation of pantoprazole racemates is achieved, with the separation time within 10 minutes and the resolution is greater than 15, which simplifies the preparation process and improves the separation efficiency.
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Abstract
Description
Technical Field
[0001] The invention relates to a method for resolving a chiral drug racemate, in particular to a capillary electrochromatography method for resolving a pantoprazole racemate. Background Art
[0002] Pantoprazole is a benzimidazole derivative, which is mainly used clinically for the treatment of peptic ulcer, upper gastrointestinal bleeding, reflux esophagitis and other diseases. Pantoprazole contains a chiral central sulfur atom in its molecular structure, and there are two enantiomers, R and S. Among them, L-pantoprazole has a significant anti-ulcer effect, which is stronger than the dextrorotatory pantoprazole. Therefore, the research and development of single enantiomers of pantoprazole has become a hot topic.
[0003] Capillary electrochromatography is a new type of efficient, fast, miniature column separation method developed in the past decade, which uses electroosmotic flow to drive the mobile phase and charged substances, and then achieves separation based on the difference in adsorption, distribution equilibrium constants and electrophoretic mobility between the stationary phase and the mobile phase. It combines the high efficiency of capillary electrophoresis and the high selectivity of liquid chromatography, and has been widely used in the separation of chiral drugs.
[0004] The capillary stationary phase is the core of capillary electrochromatography technology. According to the existence form of the stationary phase, the capillary electrochromatographic column can be divided into a packed column, a monolithic column and an open-tube column. The open-tube column is a capillary electrochromatographic column with a stationary phase coated or bonded on the inner wall of the capillary. The present invention prepares a novel chiral open-tube capillary electrochromatographic column and is used for separating pantoprazole racemate. Summary of the invention
[0005] The purpose of the present invention is to provide a capillary electrochromatographic method for resolving pantoprazole racemate, which adopts a chiral open-tube capillary electrochromatographic column to resolve pantoprazole racemate, and provides technical support for the research and development of pantoprazole single enantiomer drugs.
[0006] The objective of the present invention is achieved through the following technical solutions: A capillary electrochromatographic method for resolving pantoprazole racemates, wherein pyromellitic acid-BD-CH3-L-cysteine is used as a chiral selector, which is coated on the inner wall of a capillary by a physical coating method to prepare a chiral open-tube capillary electrochromatographic column. The pantoprazole enantiomers are resolved by a capillary electrochromatograph.
[0007] The specific separation steps are as follows: a. Column making method: (1) Cut an uncoated quartz capillary (inner diameter 50 mm) to a length of 53 cm and an effective length of 45 cm. Rinse it with pure methanol, distilled water, 1M NaOH, distilled water, anhydrous ethanol, and distilled water, respectively, and blow dry with nitrogen for later use.
[0008] (2) Dissolve dopamine and pyromellitic acid-BD-CH3-L-cysteine in a 10 mM Tris-HCL (pH=8.5) solution at a concentration of 4 mg / ml and inject into the activated capillary column at a flow rate of 0.5 ml / h for a coating time of 2 h. Seal the column and place at room temperature for 24 h.
[0009] b. Electrochromatographic separation conditions: The background electrolyte was 40 mM Tris-H3PO4, pH 7.0, the separation voltage was 15 kV, and the UV detection wavelength was 290 nm.
[0010] The advantages and effects of the present invention are: The present invention provides a chiral open-tube capillary electrochromatography method for resolving pantoprazole racemates, wherein pyromellitic acid-BD-CH3-L-cysteine is used as a chiral selector and coated on the inner wall of a capillary, and pantoprazole enantiomers are resolved by a capillary electrochromatograph. The chiral open-tube capillary electrochromatographic column prepared by the present invention has a simple preparation method and high separation efficiency. BRIEF DESCRIPTION OF THE DRAWINGS
[0011] Figure 1 The capillary electrochromatogram of the pantoprazole racemate separation of the present invention. DETAILED DESCRIPTION
[0012] The present invention will be described in detail below with reference to the accompanying drawings.
[0013] Attached Figure 1 Capillary electrochromatogram for the separation of pantoprazole racemate, with a separation time of less than 10 minutes and a resolution greater than 15. Embodiment 1
[0014] (1) Cut an uncoated quartz capillary (inner diameter 50 cm) to a length of 53 cm and an effective length of 45 cm. Rinse it with pure methanol, distilled water, 1M NaOH, distilled water, anhydrous ethanol, and distilled water, respectively, and blow dry with nitrogen for later use.
[0015] (2) Dissolve dopamine and pyromellitic acid-BD-CH3-L-cysteine in a 10 mM Tris-HCL (pH=8.5) solution at a concentration of 4 mg / ml. Rinse the activated capillary column with distilled water, and then perfuse the mixed solution into the capillary column at a perfusion flow rate of 0.5 ml / h and a coating time of 2 h. Seal the column and place it at room temperature for 24 h.
[0016] (3) Electrochromatographic separation conditions: background electrolyte was 40 mM Tris-H3PO4, pH was 7.0, separation voltage was 15 kV, and detection wavelength was 290 nm.
[0017] (4) Take a 1 mg / mL pantoprazole racemate sample, inject for 10 s, and record the capillary electrochromatogram. The electrochromatogram of pantoprazole racemate separation is shown in the attached figure. Figure 1 As shown, the pantoprazole racemate is resolved within 10 minutes with a resolution greater than 15.
Claims
1. A capillary electrochromatographic method for resolving pantoprazole racemate, characterized in that: The method adopts a physical coating method to coat a chiral selector onto the inner wall of a capillary, uses pyromellitic acid-BD-CH3-L-cysteine as a chiral selector, prepares a chiral open-tube capillary electrochromatographic column, and then uses a high-efficiency capillary electrophoresis instrument to separate the pantoprazole racemate; The specific separation steps are as follows: a. Column making method: (1) Cut an uncoated quartz capillary (inner diameter 50 μm) to a length of 53 cm and an effective length of 45 cm; rinse the capillary with pure methanol, distilled water, 1 M NaOH, distilled water, anhydrous ethanol, and distilled water in sequence, and blow dry with nitrogen for later use; (2) Dopamine and pyromellitic acid-BD-CH3-L-cysteine were mixed and dissolved in 10 mmol tris-HCl (pH=8.5) solution at a concentration of 4 mg / ml. The activated capillary was coated with this solution for 2 h, sealed, and left at room temperature for 24 h. b. Electrochromatographic separation conditions: The background electrolyte was 40 mM Tris-H3PO4, pH 7.0, the separation voltage was 15 kV, and the detection wavelength was 290 nm.