Method for separating canagliflozin five-membered-ring impurity enantiomer through high performance liquid chromatography

A high-performance liquid chromatography, five-membered ring technology, applied in the direction of material separation, analysis materials, measuring devices, etc., can solve problems such as difficult separation, inability to analyze structures and accurate quantitative research, and achieve high preparation efficiency, high degree of automation, The effect of high yield

Active Publication Date: 2016-12-14
JIANGSU DEYUAN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] Since canagliflozin must strictly control the content of the by-product R, S-configuration five-membered ring impurity produced during its synthesis process, the R, S-configuration five-membered ring impurity mixture is difficult to separate by conventional methods, and cannot be separated. For structural analysis and accurate quantitative research, it is particularly important to develop a liquid chromatography resolution method for R, S-configuration five-membered ring impurities

Method used

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  • Method for separating canagliflozin five-membered-ring impurity enantiomer through high performance liquid chromatography
  • Method for separating canagliflozin five-membered-ring impurity enantiomer through high performance liquid chromatography
  • Method for separating canagliflozin five-membered-ring impurity enantiomer through high performance liquid chromatography

Examples

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Embodiment 1

[0018] Example 1, a method for splitting canagliflozin five-membered ring impurity enantiomers by high performance liquid chromatography: dissolving the raw material five-membered ring impurity enantiomer mixture in an organic solvent to a concentration of 0.1 mg / ml; using high-efficiency liquid A phase chromatograph uses an amylose-type chiral column as a chromatographic column, and uses a mixture of n-hexane and ethanol as a mobile phase for resolution and preparation. The amylose-type chiral column is a bonded chiral chromatography column CHIRALPAK IE. The organic solvent is selected from one of absolute ethanol, n-hexane, ethanol, and methanol; the flow rate of the mobile phase is 1.0 mL / min, the temperature of the chromatographic column is 25° C., and the detection wavelength is 220 nm. The injection volume is 2 μL. The mobile phase is calculated by volume percentage, n-hexane: absolute ethanol is 40:60.

Embodiment 2

[0019] Example 2, a method for splitting canagliflozin five-membered ring impurity enantiomers by high-performance liquid chromatography: dissolving the raw material five-membered ring impurity enantiomer mixture in an organic solvent to a concentration of 25 mg / ml; using high-performance liquid phase The chromatograph uses an amylose-type chiral column as a chromatographic column and uses a mixture of n-hexane and ethanol as a mobile phase for resolution and preparation. The amylose-type chiral column is a bonded chiral chromatography column CHIRALPAK IE. The filler is preferably amylose-tris(3,5-dichlorophenylcarbamate) covalently bonded to the surface of the silica gel.

[0020] The organic solvent is selected from the mixed solvent of absolute ethanol, n-hexane, ethanol and methanol. The flow rate of the mobile phase is 70mL / min, the temperature of the chromatographic column is 40°C, and the detection wavelength is 290 nm. The injection volume is 10mL. The mobile phase ...

Embodiment 3

[0021] Example 3, a method for splitting canagliflozin five-membered ring impurity enantiomers by high-performance liquid chromatography: dissolving the raw material five-membered ring impurity enantiomer mixture in an organic solvent to a concentration of 5 mg / ml; using high-performance liquid phase The chromatograph uses an amylose-type chiral column as a chromatographic column and uses a mixture of n-hexane and ethanol as a mobile phase for resolution and preparation. The amylose-type chiral column is a bonded chiral chromatography column CHIRALPAK IE.

[0022] Described organic solvent is selected from three kinds of mixed solvents in absolute ethanol, normal hexane, ethanol, methanol.

[0023] The flow rate of the mobile phase is 10 mL / min, the temperature of the chromatographic column is 30° C., and the detection wavelength is 280 nm. The injection volume is 1 mL. The mobile phase is calculated by volume percentage, n-hexane: absolute ethanol is 50:50.

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Abstract

The invention discloses a method for separating a canagliflozin five-membered-ring impurity enantiomer through high performance liquid chromatography. The method comprises the steps that a raw material five-membered-ring impurity enantiomer mixture is dissolved in an organic solvent till the concentration is up to 0.1-25 mg / ml; a high performance liquid chromatograph is adopted, and an amylose chiral column serves as a chromatographic column and a mixed liquid prepared from n-hexane and ethanol serves as a mobile phase to perform separating preparation. The canagliflozin five-membered-ring impurity enantiomer separated and prepared by adopting the method is high in yield and can serve as a reference substance for drug research and development, and the purity can be 98% or above. The method effectively achieves separation and preparation of R and S configurations in the five-membered-ring impurity enantiomer, and the separation degree can be 2.6 or above. The automation degree of high performance liquid chromatography separation is high, and the preparation efficiency is high.

Description

technical field [0001] The invention relates to a separation technology of chiral impurities in medicines, in particular to a method for separation of canagliflozin five-membered ring impurity enantiomers by high performance liquid chromatography, which belongs to the technical field of medicine. Background technique [0002] Canagliflozin is the first SGLT2 inhibitor approved by the FDA for the treatment of type 2 diabetes in adult patients. It is a new sodium-glucose cotransporter 2 (SGLT2) inhibitor drug, which inhibits renal Glucose reabsorption increases glucose excretion, thereby reducing elevated blood glucose levels in diabetic patients. [0003] Since canagliflozin must strictly control the content of the by-product R, S-configuration five-membered ring impurity produced during its synthesis, the R, S-configuration five-membered ring impurity mixture is difficult to separate by conventional methods, and cannot be separated. To carry out structural analysis and accu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02G01N30/06
CPCG01N30/02G01N30/06
Inventor 杨汉跃董淑波王建涛陈学民郑家通
Owner JIANGSU DEYUAN PHARMA
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