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Method for determining roflumilast related substances by high performance liquid chromatography

A technology of high performance liquid chromatography and related substances, which is applied in the field of determination of related substances of roflumilast by high performance liquid chromatography, can solve the problems that the detection method needs to be improved, and achieve the improvement of drug safety, simple and fast method, and improvement of work efficiency Effect

Inactive Publication Date: 2018-07-06
SHANDONG ACADEMY OF PHARMACEUTICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] So far, Roflumilast has not been included in statutory standards such as European Pharmacopoeia, United States Pharmacopoeia, British Pharmacopoeia, Japanese Pharmacopoeia, and Chinese Pharmacopoeia; the detection methods of related substances in published relevant literature and patents still need to be improved

Method used

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  • Method for determining roflumilast related substances by high performance liquid chromatography
  • Method for determining roflumilast related substances by high performance liquid chromatography
  • Method for determining roflumilast related substances by high performance liquid chromatography

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1 System suitability test of the detection method of the present invention.

[0047] Diluent: 0.005mol / L ammonium dihydrogen phosphate solution (adjust the pH value to 3.5 with phosphoric acid)-methanol-acetonitrile (41:31:28).

[0048] Blank solution: diluent.

[0049] Preparation of impurity reference substance stock solution: take appropriate amount of impurity A, impurity B, impurity C, impurity D, impurity E, impurity F and impurity G reference substance, weigh them accurately, dissolve them with diluent respectively and quantitatively dilute to make each 1ml Containing 500μg of the solution, shake well, that is.

[0050] Preparation of impurity localization solution: Take an appropriate amount of the above-mentioned impurity reference substance stock solution, quantitatively dilute with diluent respectively to make a solution containing 10 μg per 1 ml, shake well, and obtain.

[0051]Preparation of system suitability solution: Take about 5 mg of roflumil...

Embodiment 2

[0056] Example 2 The specificity test of the detection method of the present invention.

[0057] The forced degradation test is to simulate the strong degradation conditions of strong acid, strong alkali, oxidation, light and high temperature to accelerate the destruction of roflumilast. Validity and applicability of analytical methods.

[0058] In order to better examine the specificity and stability of this method, forced degradation tests of acid, alkali, oxidation, light and high temperature were designed.

[0059] Acid-forced degradation test: take about 25mg of roflumilast, weigh it accurately, put it in a 50ml measuring bottle, add 5ml of acetonitrile and shake to dissolve, add 2ml of 1mol / L hydrochloric acid solution, shake well, put it in a water bath at 80°C for 3.5h to destroy , let it cool, add 1mol / L sodium hydroxide solution to neutralize, dilute to the mark with diluent, shake well, filter, take 10μl and inject it into the liquid chromatograph, record the chrom...

Embodiment 3

[0065] Example 3 Detection limit and quantification limit of the detection method of the present invention.

[0066] For related substances, the detection limit and quantitation limit are determined according to the signal-to-noise ratio method. Dilute the impurity reference substance stock solution of known concentration in Example 2 to a low-concentration sample, compare the measured signal with the baseline noise, and calculate the amount that can be reliably detected, with a signal-to-noise ratio of about 3:1, 10 :1 Calculate the detection limit and limit of quantification of roflumilast and each impurity respectively, and the results are shown in Table 3.

[0067] Table 3 The results of detection limit and quantitation limit

[0068]

[0069]

[0070] As can be seen from Table 3, the sensitivity of the method of the present invention is higher.

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Abstract

The invention belongs to the field of analytical chemistry, and particularly relates to a method for determining a roflumilast related substance of by high performance liquid chromatography, wherein the analytical conditions of the method are as follows: using octadecylsilane bonded silica gel as a stationary phase for a chromatographic column, using a mixture of an ammonium dihydrogen phosphate solution and an organic solvent as a mobile phase for isocratic elution. Compared with the prior art, the method has the following advantages and positive effects: impurities which may exist in roflumilast can be effectively separated and quantitatively determined, the specificity is strong, the sensitivity is high, the accuracy is good, and the method can effectively control the product quality ofthe roflumilast and preparations of the roflumilast, drug safety can be improved, and a basis is provided for formulation of quality standards of the roflumilast and the preparations of the roflumilast.

Description

technical field [0001] The invention belongs to the field of analytical chemistry, and in particular relates to a method for determining related substances of roflumilast by high performance liquid chromatography. Background technique [0002] Chronic obstructive pulmonary disease (COPD) is a common disease characterized by persistent airflow limitation and one of the diseases with the highest morbidity and mortality worldwide. As a phosphodiesterase 4 (PDE-4) inhibitor, roflumilast can block the transmission of inflammatory response signals, reduce the release of inflammatory mediators, and then inhibit the damage to lung tissue caused by respiratory diseases such as COPD. [0003] The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) approved Forest's roflumilast tablets on March 1, 2011 and February 28, 2011, respectively, for reducing the symptoms of severe chronic obstructive pulmonary disease. The frequency of attacks or exacerbations, i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02
CPCG01N30/02
Inventor 张云孙玲王立立孙晋瑞
Owner SHANDONG ACADEMY OF PHARMACEUTICAL SCIENCES
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