Method for assaying impurities in apremilast and preparations thereof through liquid chromatography

A liquid chromatography and impurity technology, applied in the field of analytical chemistry, can solve the problems of difficulty in effectively separating apremilast from impurities, affecting the quality control of apremilast and its preparations, increasing the difficulty of detection, etc., and achieving high column efficiency, Enhanced retention and improved resolution

Active Publication Date: 2016-05-18
CHONGQING PHARMA RES INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] It can be seen that there are many related substances of Apremilast, and their structures are similar, which makes separation difficult. In addition, the polarities of each impurity are different, and there are intermediates IV and IP1 with large polar differences, and some have similar polarities. IP9 and IP10, as well as IP1 and IP14, on the premise of satisfying the separation between Apremilast and various impurities, it also needs to meet the separation between impurities, which makes the detection more difficult
It is difficult to achieve effective separation between apremilast and impurities and between impurities and impurities by conventional detection methods, which will affect the quality control of apremilast and its preparations

Method used

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  • Method for assaying impurities in apremilast and preparations thereof through liquid chromatography
  • Method for assaying impurities in apremilast and preparations thereof through liquid chromatography
  • Method for assaying impurities in apremilast and preparations thereof through liquid chromatography

Examples

Experimental program
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Effect test

Embodiment 1

[0052] Apparatus and conditions

[0053] Agilent1200 liquid chromatograph and ChemStation; automatic sampling; AgilentEclipsePlusC18 column (5mm, 250×4.6mm) as the separation chromatographic column; UV detector wavelength: 230nm; mobile phase: 0.01mol / L potassium dihydrogen phosphate solution (Adjust the pH value to 2.3 with phosphoric acid solution) as mobile phase A, methanol-acetonitrile (45:55; V / V) as mobile phase B, gradient elution; 0 minutes, mobile phase A is 95% (V / V) ), mobile phase B is 5% (V / V); 0 minutes to 8 minutes, mobile phase A linearly decreases to 80% (V / V), mobile phase B linearly increases to 20% (V / V); 8 minutes To 40 minutes, mobile phase A linearly decreases to 20% (V / V), mobile phase B linearly increases to 80% (V / V); 40 minutes to 50 minutes, mobile phase A is 20% (V / V), Mobile phase B is 80% (V / V); 50 minutes to 53 minutes, mobile phase A linearly increases to 95% (V / V), mobile phase B linearly decreases to 5% (V / V); 53 minutes to 60 Minutes, mobile...

Embodiment 2

[0060] Determination of impurities in the API of API.

[0061] Take about 10mg of Apster, accurately weigh it, put it in a 50ml measuring flask, add diluent (acetonitrile: water = 20: 80V / V) ultrasonic treatment to dissolve and dilute to the mark, shake it, as the test solution; Accurately weigh 10 mg of the aprester reference substance, put it in a 50 ml measuring flask, add diluent (acetonitrile: water = 20: 80V / V) ultrasonic treatment to dissolve and dilute to the mark, shake it, as a control solution; follow the example Perform liquid chromatography analysis under the chromatographic conditions of 1. If there are impurity peaks (except solvent peaks) in the chromatogram of the test solution, the peak area after the known impurity is multiplied by the correction factor shall not be greater than 1 / 2 of the main peak area of ​​the control solution ( 0.5%), the peak area of ​​a single impurity shall not be greater than 1 / 2 (0.5%) of the main peak area of ​​the control solution, a...

Embodiment 3

[0063] Liquid chromatography was used to determine the impurities in Apexit tablets.

[0064] Take an appropriate amount of this product (approximately equivalent to 10mg of Aplast), put it in a 50ml measuring bottle, add diluent (acetonitrile: water = 20: 80V / V) ultrasonic treatment to dissolve and dilute to the mark, shake it, as a test Product solution; another accurately weighed 10mg of apreste reference substance, put it in a 50ml measuring flask, add diluent (acetonitrile: water = 20: 80V / V) ultrasonic treatment to dissolve and dilute to the mark, shake it, as a control solution ; In addition, take an appropriate amount of blank excipients according to the prescription ratio, prepare the blank excipients for the test solution in the same way as the test solution; perform liquid chromatography analysis according to the chromatographic conditions of Example 1, if there are impurity peaks in the chromatogram of the test solution (Except solvent peak and blank auxiliary materia...

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Abstract

The invention discloses a method for separating and assaying impurities in apremilast and preparations thereof through liquid chromatography. In the method, octadecylsilane chemically bonded silica is employed as a filler in a chromatography column; a buffer solution is employed as a mobile phase A; and a methanol-acetonitrile mixture solvent is employed as a mobile phase B, wherein a gradient elution method is employed in the mobile phases to assay the impurities in apremilast and the preparations thereof. The method can effectively separate and assay unknown impurities and known impurities from the apremilast. The method has strong specificity, is high in accuracy, is easy to use and can be used for effectively control the quality of the apremilast and preparations thereof.

Description

Technical field [0001] The present invention is a method of analyzing the field of chemistry, which involves the method of determining the impurities in Aprus and the preparation of the liquid chromatography method. Background technique [0002] MethylnalTrexoneBromide is a inhibitor of a phosphate-4 (PDE-4), its molecular formula is C 22 H 24 N 2 O 7 S, the structure of the structure is shown in the following formula (A) compound. [0003] Apuster's chemical name is: (S) -2- [1- (3-ethyl-4-methoxybenzhenyl) -2-methyl-inferior ethyl]Globoline-1,3-dione.In the process of synthesizing this compound, several important intermediates and unknown impurities may affect the purity and quality of the drug due to incomplete removal.It is usually mentioned in substances (that is, impurities).There are eight known impurities in the synthesis of Afferster, which are: starting raw material SM2, which see the following formula (B); intermediate II, the structure of the structure (C); the interm...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02
Inventor 熊娟代广会万娟张道林
Owner CHONGQING PHARMA RES INST
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