Method for separating and analyzing optical isomers of bedaquiline

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: 2019-02-26
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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  • Method for separating and analyzing optical isomers of bedaquiline
  • Method for separating and analyzing optical isomers of bedaquiline
  • Method for separating and analyzing optical isomers of bedaquiline

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Instruments 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°C;

[0038] Wavelength: 226nm;

[0039] Flow rate: 0.1mL / min;

[0040] Injection volume: 1 μL.

[0041] Experimental procedure

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

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

[0044] System suitability solution: Weigh 10mg of (1R,2S)-bedaquiline into a 10mL volumetric flask, pipette 1.0mL of (1S,2R)-bedaquiline stock solution into this volumetric flask, add methanol to dissolve ...

Embodiment 2

[0050] Instruments 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°C;

[0054] Wavelength: 226nm;

[0055] Flow rate: 0.08mL / min;

[0056] Injection volume: 1 μL.

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

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

[0059]Take 1 μL of the test solution and (1R,2S)-bedaquiline self-contrast solution respectively, perform high-performance liquid chromatography analysis according to the above conditions, and record the chromatograms. The content of (1S, 2R)-bedaquiline was calculated by adding a correction factor to the self-control method, and the content was 0.2%.

[0060] see attached r...

Embodiment 3

[0062] Instruments 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°C;

[0066] Wavelength: 226nm;

[0067] Flow rate: 0.09mL / min;

[0068] Injection volume: 1 μL.

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

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

[0071] Take 1 μL of the test solution and (1R,2S)-bedaquiline self-contrast solution respectively, perform high-performance liquid chromatography analysis according to the above conditions, and record the chromatograms. The content of (1S, 2R)-bedaquiline was calculated by adding a correction factor to the self-control method, 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 bedaquiline optical isomers, belonging to the field of liquid chromatography. Background technique [0002] (1R, 2S)-bedaquiline is a multidrug-resistant tuberculosis drug with the molecular formula C 32 h 31 BrN 2 o 2 , 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 two chiral centers, one enantiomer and two diastereomers. The two diastereoisomers are easier to separate, but the enantiomer (1S,2R)-bedaquiline is more difficult to separate, which may remain in the drug through subsequent reactions and affect the quality of the drug. Therefore, for the enantiomeric impurities of (1R,2S)-bedaquiline, quality control is required during the drug synthesis process. Controlling the content of enantiomers in (1R,2S)-bedaquiline is of great significance f...

Claims

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Application Information

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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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