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A method for separating and analyzing bedaquiline optical isomers

A technology of optical isomers and bedaquiline, applied in the field of liquid chromatography, can solve problems such as difficult quality control

Active Publication Date: 2021-01-19
WUHAN WUYAO SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, the separation of optical isomers containing chiral carbon atoms has always been a difficult point in quality control during the synthesis and preparation of chiral drugs

Method used

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  • A method for separating and analyzing bedaquiline optical isomers
  • A method for separating and analyzing bedaquiline optical isomers
  • A method for separating and analyzing bedaquiline optical isomers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034]Apparatus and conditions

[0035]Chromatographic column: Daicel CHIRALPAKZWIX(+) (4.6*150mm, 3μm);

[0036]Mobile phase: 2.6mL diethylamine, 1.9mL formic acid to 1000mL methanol;

[0037]Column temperature: 12℃;

[0038]Wavelength: 226nm;

[0039]Flow rate: 0.1mL / min;

[0040]Injection volume: 1μL.

[0041]Experimental steps

[0042](1S,2R)-Betaquinoline stock solution: Weigh 10mg of (1S,2R)-Betaquinoline, place in a 10mL measuring flask, dilute to the mark with methanol, shake well, and then pipette 1mL into 100mL volume In the bottle, dilute with methanol to a constant volume.

[0043]Test solution: Weigh (1R, 2S)-Bedaquinoline 10mg, accurately weigh it, put it in a 20mL measuring flask, add methanol to dissolve and dilute to the mark, shake well.

[0044]System suitability solution: Weigh 10 mg of (1R, 2S)-Betaquinoline into a 10mL volumetric flask, pipette 1.0 mL of (1S, 2R)-Betaquinoline stock solution into this volumetric flask, add methanol to dissolve and dilute To the mark, shake well.

[0045](1R, 2...

Embodiment 2

[0050]Apparatus and conditions

[0051]Chromatographic column: Daicel CHIRALPAKZWIX(+) (4.6*150mm, 3μm);

[0052]Mobile phase: 2.6mL diethylamine, 1.9mL formic acid to 1000mL methanol;

[0053]Column temperature: 12℃;

[0054]Wavelength: 226nm;

[0055]Flow rate: 0.08mL / min;

[0056]Injection volume: 1μL.

[0057]The experimental procedure is the same as in Example 1.

[0058]Measure 1μL of the system suitability solution, inject it into the liquid chromatograph, and record the chromatogram. The resolution of (1S,2R)-bedaquinoline peak and (1R,2S)-bedaquinoline peak is greater than 1.5.

[0059]Take 1μL each of the test solution and (1R,2S)-bedaquinoline self-control solution, perform HPLC analysis under the above conditions, and record the chromatogram. The content of (1S, 2R)-bedaquinoline was calculated according to the self-control method with correction factor, and the content was 0.2%.

[0060]The results are attachedfigure 2 , The peak 1 in the figure is the isomer (1R,2S)-bedaquinoline, and the peak 2 is...

Embodiment 3

[0062]Apparatus and conditions

[0063]Chromatographic column: Daicel CHIRALPAKZWIX(+) (4.6*150mm, 3μm);

[0064]Mobile phase: 2.6mL diethylamine, 1.9mL formic acid to 1000mL methanol;

[0065]Column temperature: 12℃;

[0066]Wavelength: 226nm;

[0067]Flow rate: 0.09mL / min;

[0068]Injection volume: 1μL.

[0069]The experimental procedure is the same as in Example 1.

[0070]Measure 1μL of the system suitability solution, inject it into the liquid chromatograph, and record the chromatogram. The resolution of (1S,2R)-bedaquinoline peak and (1R,2S)-bedaquinoline peak is greater than 1.5.

[0071]Take 1μL each of the test solution and (1R,2S)-bedaquinoline self-control solution, perform HPLC analysis under the above conditions, and record the chromatogram. The content of (1S, 2R)-bedaquinoline was calculated according to the self-control method with correction factor, and the content was 0.2%.

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Abstract

The invention relates to a method for separating and analyzing optical isomers of bedaquiline, belonging to the field of liquid chromatography. The method is reversed-phase high-performance liquid chromatography; a selected chromatographic column is an amphoteric ion exchange chiral column; the column temperature of the chromatographic column is 9-20 DEG C; a mobile phase is a mixed solution of 2mL to 3 mL of diethylamine, 1.5 mL to 2.5 mL of formic acid and 1000 mL of methanol; the velocity of the mobile phase is 0.08 mL / min to 0.12 mL / min; a detection wavelength is 220 nm to 230 nm; the resolution of a (1S, 2R)-bedaquiline peak and a (1R, 2S)-bedaquiline peak on a chromatogram is greater than 1.5. The method of the invention can effectively separate (1R, 2S)-bedaquiline and / or (1S, 2R)-bedaquiline, and / or detect the purity and / or the content of (1R, 2S)-bedaquiline and the purity of (1S, 2R)-bedaquiline.

Description

Technical field[0001]The invention relates to a method for separating and analyzing bedaquinoline optical isomers, and belongs to the field of liquid chromatography.Background technique[0002](1R, 2S)-Betaquinoline is a multi-drug resistant tuberculosis drug, its molecular formula is C32H31BrN2O2, The chemical name is (1R, 2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-dimethylamino-1-phenyl-2-(1-naphthyl)- 2-butanol, the structural formula is[0003][0004]The molecule contains 2 chiral centers, one enantiomer and two diastereomers. The two diastereomers are easier to separate, but the enantiomer (1S,2R)-bedaquinoline is more difficult to separate. It can remain in the drug through subsequent reactions and affect the quality of the drug. Therefore, the enantiomeric impurities of (1R,2S)-bedaquinoline need to be quality controlled during the drug synthesis process. Controlling the content of enantiomers in (1R, 2S)-bedaquinoline is of great significance for improving the quality of the drug a...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): G01N30/89
CPCG01N30/89
Inventor 曾薇乔春莲郭亚兵杨波
Owner WUHAN WUYAO SCI & TECH
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