Detection method for determining chloroacetic acid residues in cinepazide maleate intermediate through HPLC method

A technology for the detection of cinepazide maleate and its detection method, which is applied in the field of detection of chloroacetic acid residues in cinepazide maleate intermediates by HPLC, and can solve the problem of weak ultraviolet absorption, low boiling point of chloroacetic acid, and hydrocarbon-containing The ratio is small and other problems, to achieve high accuracy of detection results, to overcome the content of chloroacetic acid, the effect of accurate and reliable content

Active Publication Date: 2020-12-01
HARMONIA TESTING TECH TIANJIN LTD
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Problems solved by technology

The derivatization method is also commonly used in the detection of halogenated hydrocarbons, but its operation is relatively cumbersome
[0004] Chinese patent CN 110988151A pointed out in the background technology that due to the low boiling point of chloroacetic acid, small molecular weight, weak ultraviolet absorption and small proportion of hydrocarbons, it is difficult to use the commonly used detection methods GC-FID, HPLC-UV, GC-MS detection test Low concentration limit of chloroacetic acid in samples
However, this detection method has high requirements for instruments, and requires the combination of liquid chromatography and mass spectrometry, and the operation process is cumbersome and complicated.

Method used

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  • Detection method for determining chloroacetic acid residues in cinepazide maleate intermediate through HPLC method
  • Detection method for determining chloroacetic acid residues in cinepazide maleate intermediate through HPLC method
  • Detection method for determining chloroacetic acid residues in cinepazide maleate intermediate through HPLC method

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Experimental program
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Effect test

Embodiment 1

[0043] The detection of chloroacetic acid content in embodiment 1 sample

[0044] According to the consumption of cinepazide maleate intermediate, the limit requirement of chloroacetic acid in this product is 62.5ppm. Use HPLC method to detect residual amount of chloroacetic acid in this product, the signal-to-noise ratio is 33 when the concentration of chloroacetic acid reference substance solution is 5 μ g / ml, it is regarded as 100% limit level solution, must not cross 62.5ppm according to its limit requirement, sample concentration is 80mg / ml. Such a high concentration of sample concentration will greatly damage the life of the instrument and chromatographic column, and the injection concentration should be reduced as much as possible. This product has low solubility in water, and its solubility in acetonitrile is as high as 200mg / ml. Therefore, using the difference in solubility of this product, first use a small amount of good solvent (acetonitrile) to completely dissolv...

Embodiment 2

[0065] Embodiment 2 specificity experiment

[0066] Investigate whether the diluent and other components of the sample solution interfere with the chromatographic peak of chloroacetic acid.

[0067] Chloroacetic acid reference substance stock solution (50 μg / ml): Take about 5 mg of chloroacetic acid reference substance, weigh it accurately, put it in a 100ml measuring bottle, add acetonitrile to dissolve and dilute to the mark, shake well, and obtain.

[0068] Chloroacetic acid reference substance solution: Accurately measure 1ml of chloroacetic acid reference substance stock solution, put it in a 10ml measuring bottle, add water to dilute to the mark, and shake well to obtain.

[0069] Sample solution: Accurately weigh 81.7mg of the sample, put it in a 1.5ml EP tube, add 400μl of acetonitrile, vortex to dissolve it completely, add 600μl of water, vortex, centrifuge to get the supernatant, and get ready.

[0070] Sample spike solution: Accurately weigh 82.5mg of the sample, p...

Embodiment 3

[0075] Embodiment 3 system precision experiment

[0076] Take the chloroacetic acid reference solution with a concentration of 5 μg / ml and inject it continuously for 6 times, record the chromatogram, and calculate the RSD of the peak area of ​​chloroacetic acid. The peak area RSD of chloroacetic acid obtained by six consecutive injections is listed in Table 2. It can be seen from Table 2 that the peak area RSD of chloroacetic acid is 1.0%, less than 4%. Therefore, the system precision of this method is good.

[0077] Table 2 System precision results

[0078]

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Abstract

The invention belongs to the technical field of chloroacetic acid detection, and particularly relates to a detection method for determining chloroacetic acid residues in a cinepazide maleate intermediate through an HPLC method. The method comprises the following steps: (1) preparing a reference solution; (2) preparing a sample solution; (3) performing sample injection detection in HPLC, wherein chromatographic detection conditions are as follows: chromatographic column: a silane bonding silica gel column is a high performance liquid chromatography column of a stationary phase, a mobile phase A: water-methanol-trifluoroacetic acid in a volume ratio of 96: 4: 0.1, a mobile phase B: methanol, the flow velocity of the mobile phase being 0.6-1ml/min, the column temperature of the chromatographic column is 33-37 DEG C, the sample size is 20mu l, and the detection wavelength is 212-216nm; and (4) calculating the content of chloroacetic acid: calculating the content of chloroacetic acid according to the peak area through an external standard method. The method has the beneficial effects that the chloroacetic acid is detected by using the HPLC method, the operation is simple, and the problems in the prior art are solved.

Description

technical field [0001] The invention belongs to the technical field of chloroacetic acid detection, in particular to a method for detecting residual chloroacetic acid in an intermediate of cinepazide maleate by HPLC. Background technique [0002] Cinepazide maleate chemical name: (E)-1-{4-[(3',4',5'-trimethoxycinnamoyl)]1-1piperazine}acetylpyrrolidine maleic butene Diacid salts, which can be used to treat cerebrovascular diseases and cardiovascular diseases, often contain chloroacetic acid as an impurity, which is one of the genotoxic impurities. Genotoxic impurities refer to positions that can directly or indirectly damage DNA, cause gene mutation or have a tendency to cause cancer. Chloroacetic acid is one of the raw materials used in the synthesis process of the cinepazide maleate intermediate, and the present invention further ensures the safety of the drug by strictly controlling the content of chloroacetic acid in the cinepazide maleate intermediate . [0003] In re...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02G01N30/04
CPCG01N30/02G01N30/04G01N2030/047
Inventor 张娜李安平张志英王梁
Owner HARMONIA TESTING TECH TIANJIN LTD
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