Method for detecting residual impurities in entacapone

A technology of residual impurities and entacapone, which is applied in the field of detection of residual impurities in entacapone, can solve the problems of effective detection of N,N-diethylcyanoacetamide, etc., and achieves high sensitivity, high precision, Easy to use effect

Active Publication Date: 2022-06-03
河北广祥制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] Aiming at the problem that N,N-diethylcyanoacetamide in entacapone cannot be effectively detected in the prior art, the present invention provides a method for detecting residual impurities in entacapone

Method used

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  • Method for detecting residual impurities in entacapone
  • Method for detecting residual impurities in entacapone
  • Method for detecting residual impurities in entacapone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Exclusive test:

[0058] Blank solution: pure water.

[0059] Reference substance stock solution: take an appropriate amount of N,N-diethylcyanoacetamide, accurately weigh it, and prepare a N,N-diethylcyanoacetamide solution containing about 2.00 μg per 1 mL of water, as the reference substance stock solution .

[0060] Reference substance solution: Take an appropriate amount of the reference substance stock solution, accurately weigh it, and dilute it with water to about 100ng of N,N-diethylcyanoacetamide solution per 1mL, as the reference substance solution.

[0061] Test solution: take about 25.00mg of entacapone raw material, accurately weigh it, put it in a 250mL volumetric flask, add water to dissolve and dilute to the mark, as the test solution.

[0062] Test substance plus reference substance solution: take about 25.00mg of entacapone raw material, accurately weigh it, put it in a 250mL volumetric flask, add 12.5mL of reference substance stock solution, add wate...

Embodiment 2

[0066] Linear relationship:

[0067] Linear stock solution: take an appropriate amount of N,N-diethyl cyanoacetamide reference substance, accurately weigh it, and make a N,N-diethyl cyanoacetamide solution containing about 2.00 μg per 1 mL of water as a linear stock solution .

[0068] Linear solution: Precisely measure an appropriate amount of linear stock solution and dilute with water to a solution containing about 5.11ng, 20.44ng, 61.31ng, 102.19ng, 143.07ng and 204.38ng of N,N-diethylcyanoacetamide per 1mL, respectively. Shake well as a linear solution.

[0069] Take each linear solution, carry out HPLC-MS / MS detection, and record the chromatogram. Taking the injection concentration of N,N-diethylcyanoacetamide (ng / mL) as the abscissa and the peak area as the ordinate, draw a standard curve, such as Figure 5 ; And calculate the regression equation, the results are shown in Table 1.

[0070] Table 1 N,N-Diethylcyanoacetamide linearity test results

[0071]

[0072...

Embodiment 3

[0075] Limit of detection and limit of quantitation tests:

[0076] Reference substance stock solution: take an appropriate amount of N,N-diethylcyanoacetamide, accurately weigh it, and prepare a N,N-diethylcyanoacetamide solution containing about 2.00 μg per 1 mL of water, as the reference substance stock solution .

[0077] Reference substance solution: Take an appropriate amount of the reference substance stock solution, accurately weigh it, and dilute it with water to about 100ng of N,N-diethylcyanoacetamide solution per 1mL, as the reference substance solution.

[0078] Take the reference solution, quantitatively dilute it with water step by step, carry out HPLC-MS / MS detection, record the chromatogram, and obtain the detection limit according to the signal-to-noise ratio not less than 3:1, and according to the signal-to-noise ratio not less than 10:1, get The limit of quantification is shown in Table 2.

[0079] 6 copies of the limit of quantification solution were pre...

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Abstract

The invention relates to the technical field of pharmaceutical analysis, and discloses a method for detecting residual impurities in entacapone, and the residual impurities are N, N-diethyl cyanoacetamide. According to the method, a high performance liquid chromatography and mass spectrometry combined method is adopted for detection, and the conditions of liquid chromatography are as follows: a C18 chromatographic column is adopted, a mobile phase A is a formic acid aqueous solution with the volume concentration of 0.08%-0.12%, a mobile phase B is methanol, and gradient elution is performed; the mass spectrum conditions are as follows: an APCI ion source is adopted, a positive ion scanning mode is adopted, and quantitative ions are as follows: parent ions are 141.1 m / z, and daughter ions are 100.2 m / z; the qualitative ions are as follows: parent ions are 141.1 m / z, and daughter ions are 72.1 m / z. The method provided by the invention has the characteristics of accurate qualification, high sensitivity, high precision, good linearity and good reproducibility, is simple and convenient to operate, and is suitable for analysis and detection of the impurity N, N-diethyl cyanoacetamide in entacapone.

Description

technical field [0001] The invention relates to the technical field of drug analysis, in particular to a method for detecting residual impurities in entacapone. Background technique [0002] Entacapone is a catechol-O-methyltransferase (COMT) inhibitor, a reversible and specific COMT inhibitor that mainly acts on the periphery. It reduces the metabolism of levodopa to 3-oxo-methyldopa (3-OMD) by inhibiting the COMT enzyme, which increases the bioavailability of levodopa and increases the total amount of levodopa available in the brain. Entacapone can be used as an adjunct to levodopa / benserazide or levodopa / carbidopa for the treatment of Parkinson's disease and end-of-dose phenomena (symptom fluctuations) that cannot be controlled by the above drugs. A trace amount of residual process impurity may be produced in the entacapone raw material produced by the existing process: N,N-diethylcyanoacetamide, and its chemical structure is as follows: [0003] [0004] According t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02G01N30/06G01N30/72
CPCG01N30/02G01N30/06G01N30/72G01N2030/027
Inventor 董海峰王亚静范燕龙李彤安淼季妍张冠华牛若凡刘丹董博
Owner 河北广祥制药有限公司
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