Method for determining impurities in timolol maleate

A technology of timolol maleate and maleic acid, which is applied in the field of determination of impurities in timolol maleate, can solve the problems of large damage to the chromatographic column, incapable of qualitative analysis, limited popularity, etc., and achieve high accuracy High, improve economy and popularization, and highly targeted effect

Pending Publication Date: 2022-04-15
广东省药品检验所
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The pharmacopoeias of many countries have recorded methods for controlling impurities in timolol maleate, among which ChP2020 uses thin-layer chromatography, which has poor specificity, and USP2021 and BP2021 use high-performance liquid chromatography, which has slightly better specificity
However, in the current standards, the methods used in BP2020 and USP2021 need to purchase expensive materials (impurity reference substances)
In addition, the two methods respectively use the ion-pairing reagent sodium octane sulfonate and the peak shape improving agent trifluoroacetic acid, which cause great damage to the chromatographic column and cannot be directly used for qualitative analysis by mass spectrometry, which limits the popularity of the method.

Method used

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  • Method for determining impurities in timolol maleate
  • Method for determining impurities in timolol maleate
  • Method for determining impurities in timolol maleate

Examples

Experimental program
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Effect test

Embodiment 1

[0078] A method for measuring impurities in timolol maleate, comprising the following steps:

[0079] Take 50 mg of timolol maleate, add 1 ml of 5M sodium hydroxide solution, heat in a water bath at 75°C for 30 min, cool, add 1 ml of 5M hydrochloric acid solution, add solvent (0.01M ammonium acetate aqueous solution containing 0.2% formic acid-methanol=50 : 50) diluted to 10ml, must destroy solution I;

[0080] Take 10 mg of timolol maleate and 200 mg of maleic acid, thoroughly grind and mix them evenly under the condition of avoiding light, heat in an oven at 105°C for 60 min, cool down, take 10 mg with a solvent (0.01M ammonium acetate aqueous solution containing 0.2% formic acid -Methanol=50:50) was diluted to 10ml to obtain Destruction Solution II;

[0081] Take timolol maleate, add potassium tert-butoxide in tert-butanol solution, place in 26°C water bath for 30 minutes, add solvent (0.01M ammonium acetate aqueous solution containing 0.2% formic acid-methanol=50:50) and ...

Embodiment 2

[0111] A method for measuring impurities in timalol maleate, comprising the following steps:

[0112] Wherein, the preparation method of preparing destruction solution I, destruction solution II, destruction solution III, destruction solution IV and system suitability solution is the same as that in Example 1;

[0113] The above destruction solutions I~IV and the system suitability solution, impurities B, C, D, E, F control solution (USP, batch numbers are R073G0, R090T0, R071X0, R073H0 and R102U0) respectively by quadrupole-electrostatic field track The trap was detected by a high-resolution mass spectrometer (thermo Q Exactive), the chromatographic column was ACE Excel3 C18-AR (3 μm, 150×4.6 mm), the mobile phase conditions were the same as in Example 1, and the detector was a UV-high-resolution mass spectrometry detector.

[0114] The ESI source, ion source parameters and scanning parameters are shown in Table 4. The structural formula of each impurity is shown in Example ...

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Abstract

The invention discloses a method for determining impurities in timolol maleate. The method comprises the following steps: taking a timolol maleate sample homologous with a timolol maleate sample to be detected, and reacting to obtain a destroying solution containing an impurity X; the method comprises the following steps: taking a timolol maleate sample to be detected, and preparing a test solution by using a solvent; diluting the test solution as a contrast solution; respectively carrying out liquid chromatography detection on the destroyed solution, the test solution and the contrast solution so as to calculate the content of the impurity X in the to-be-detected sample. According to the method, impurities G, B, D, E, C and 5 can be directionally damaged, the interference impurity is small, the positioning of each impurity is not influenced, an impurity reference substance is not used, an ion pair reagent and a peak shape improver are removed from a chromatographic system, the loss of a chromatographic column is relatively small, the method can be simultaneously used for liquid chromatography and liquid chromatography-mass spectrometry detection, the qualitative analysis on the impurities can be conveniently carried out at the same time, and the detection accuracy is high. The economical efficiency and the universality of the method are improved.

Description

technical field [0001] The invention belongs to the technical field of impurity detection, and in particular relates to a method for determining impurities in timolol maleate. Background technique [0002] Timolol maleate is a new generation of powerful β-receptor blocking drug, it has blocking effect on both β1 and β2 receptors, the effect strength is 8 times that of propranolol, it has no membrane stabilizing effect, no endogenous Induced sympathomimetic activity, no direct inhibition of the heart, a significant effect of lowering intraocular pressure. It is clinically used to treat hypertension, angina pectoris, tachycardia and glaucoma. It has good curative effect on mild and moderate hypertension, without obvious adverse reactions, and can be used in combination with diuretics. Long-term medication in patients with myocardial infarction can reduce the incidence of re-infarction and mortality. It has a good effect on glaucoma, especially primary and open-angle glaucom...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02
Inventor 田珩吴纯敏戴聪杨仪雪贝琦华严全鸿
Owner 广东省药品检验所
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