Method for separating timolol compound and timolol maleate related impurities and application of method

A technology of timolol maleate and timolol, which is applied to the separation of impurities related to timolol compounds and timolol maleate and its application field, can solve the problems of difficult separation of impurities and solvent volatility. Large, high-performance liquid chromatography damage and other problems, to achieve high sensitivity, strong specificity, to solve the effect of interference

Active Publication Date: 2019-07-09
WUHAN CONFORM PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The technical problem to be solved by the present invention is to overcome solvent volatility when adopting normal phase system when separating timolol maleate isomers in the prior art, and normal phase solvent is easy to cause damage to high performance liquid chromatography , related impurities in S-timolol, or the defects that related impurities in S-timolol maleate are difficult to separate, thereby providing a kind of timolol compound and related impurities in timolol maleate Separation method and its application

Method used

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  • Method for separating timolol compound and timolol maleate related impurities and application of method
  • Method for separating timolol compound and timolol maleate related impurities and application of method
  • Method for separating timolol compound and timolol maleate related impurities and application of method

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] 1. Instrument: Shimadzu LC-20AT, the detector model is SPD-M20A electronic analytical balance of Sartorius Scientific Instrument Co., Ltd., model is SECURA 125.

[0057] 2. High performance liquid chromatography conditions:

[0058] Mobile phase: methanol: acetonitrile = 10:90 (add 50mmol formic acid and 25mmol diethylamine to the mixed solution, accounting for 0.45% of the mobile phase volume)

[0059] Chromatographic column ZWIX(+)150×4mm, 4.0μm;

[0060] The detection wavelength is 298nm;

[0061] The column temperature is 25°C;

[0062] Flow rate 0.5ml / min.

[0063] 3. Measurement method:

[0064] 3.1 Accurately weigh the appropriate amount of S-timolol (manufacturer: EP, batch number: Batch3.0) and R-timolol (manufacturer: EP, batch number: Batch3.0) reference substance, add methanol to dissolve and dilute to each A solution containing 1 mg of S-timolol and 0.1 mg of R-timolol in 1 ml was used as a systemic suitability solution.

[0065] Experiments were ca...

Embodiment 2

[0080] Carry out the experiment with reference to the sample and operating method of 3.1 of Example 1, the difference is that the mobile phase is methanol: acetonitrile=15:85 (add 50mmol formic acid and 25mmol diethylamine to the mixed solution, the percentage of the amount added is 0.45%) . Obtain efficient chromatogram, the result is as follows:

[0081]

[0082] Among them, peak number 1 is maleic acid; peak number 2 is R-timolol; peak number 3 is S-timolol.

[0083] The results show that the chromatographic conditions can effectively separate S-timolol, R-timolol and maleic acid, and the peak shape is better, the baseline is more stable, and the resolution is greater than 1.5.

[0084] 3.4 Sample recovery experiment

[0085] Accuracy is obtained by adding 80%, 100% and 120% of the recovery rate of three different concentrations of R-timolol stock solution (2μg / ml) in the test solution, adding a known amount of R-timolol Lol, then measure the ratio (recovery rate) bet...

Embodiment 3

[0091] Carry out experiment with reference to the sample and operation method of 3.1 of embodiment 1, difference is that mobile phase is methyl alcohol: acetonitrile=5:95 (add 50mmol formic acid and 25mmol diethylamine in mixed solution, account for 0.45% of mobile phase volume ). Obtain high-efficiency chromatograms, the results are as follows:

[0092]

[0093] Among them, peak number 1 is maleic acid; peak number 2 is R-timolol; peak number 3 is S-timolol.

[0094] The results show that the chromatographic conditions can effectively separate S-timolol, R-timolol and maleic acid, and the peak shape is better, the baseline is more stable, and the resolution is greater than 1.5.

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Abstract

The invention discloses a method for separating a timolol compound and / or timolol maleate related impurities and application of the method. According to the method for separating the timolol compoundand / or the timolol maleate related impurities and the application of the method, a chromatographic column of which filler is silica gel bonded with quinine derivatives on the surface is applied to high performance liquid chromatography conditions to separate the timolol compound, a timolol maleate compound and the related impurities of timolol maleate. The method adopts a reversed-phase high-performance liquid phase system, the timolol compound and the related impurities of timolol maleate can be effectively separated, the accuracy is high, the sensitivity is high, and the method is environmentally friendly and can be used for quantitative detection of the timolol compound.

Description

technical field [0001] The invention relates to a method for separating timolol compounds and related impurities of timolol maleate and an application thereof. Background technique [0002] S-timolol is a non-selective potent β-blocker. No endogenous sympathomimetic activity, no local anesthetic effect, weak membrane stabilizing effect. The β-receptor blocking effect is 5-10 times that of propranolol, and the inhibitory effect on myocardial is lighter than that of propranolol. After medication, the heart rate can be slowed down, the myocardial contractility is weakened, and the myocardial oxygen consumption is reduced. [0003] [0004] From the structural formula of S-timolol, it can be seen that: S-timolol has a chiral carbon atom, and its configuration is S-type, so there is an enantiomer of R-type in timolol Construct. As we all know, only S-type timolol is the effective ingredient for treatment, while R-type timolol and its related substances must be strictly con...

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 周小顺牟东升李彤彤黄秀琴李进贺容丽刘文双
Owner WUHAN CONFORM PHARMA CO LTD
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