Method for determining aniline-type genotoxic impurities in novel solifenacin succinate crude drug

A technology of Solidium Sodium and raw materials, which is applied in the field of drug testing of Solidium Succinate New Raw Materials, to achieve the effect of reducing the use of organic solvents, reducing environmental hazards, and good repeatability

Active Publication Date: 2019-02-22
上海明捷医药科技有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] The purpose of the present invention is to solve the existing 4-chloroaniline and (-)-4'-chloroaniline tartaric acid content determination problem that there is no quality standard to check, and to provide a method for the determination of aniline in the new raw material drug of solidium succinate The method of genotoxic impurities has the advantages of short detection time, good accuracy, high precision and good repeatability

Method used

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  • Method for determining aniline-type genotoxic impurities in novel solifenacin succinate crude drug
  • Method for determining aniline-type genotoxic impurities in novel solifenacin succinate crude drug
  • Method for determining aniline-type genotoxic impurities in novel solifenacin succinate crude drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] A method for the determination of genotoxic impurities in a new raw material drug of sodium succinate, including the following steps:

[0041] S1. Prepare 4-chloroaniline and (-)-4'-chloroaniline wine with 4-chloroaniline and (-)-4'-chloroaniline tartaramic acid as the reference substance and 50% acetonitrile aqueous solution as the solvent Paraffinic acid reference substance solution, take the new sodium succinate raw material drug, and dissolve it with 50% acetonitrile aqueous solution to obtain the test solution;

[0042] S2. Prepare two 4-chloroaniline and (-)-4'-chloroaniline tartaramic acid reference solutions in parallel, and obtain 4-chloroaniline and (-)- in the reference solution by UPLC-MS method. The peak area of ​​4'-chloroaniline tartaramic acid, calculate the ratio of the peak area to the concentration of the reference solution, and obtain the response factors of 4-chloroaniline and (-)-4'-chloroaniline tartaramic acid;

[0043] S3. Take the test solution to de...

Embodiment 2

[0058] The linear range of the measurement method provided in Example 1 was investigated.

[0059] Take 10mg of 4-chloroaniline and (-)-4'-chloroaniline tartaramic acid in a 10mL volumetric flask, dissolve and dilute to the mark with 50% acetonitrile, shake well, as the reference substance stock solution 1; accurately measure Put 300μL of reference substance stock solution 1 in a 100mL volumetric flask, dilute to the mark with 50% acetonitrile, shake well, and serve as reference substance stock solution 2;

[0060] Pipette 0.05mL, 0.25mL, 0.4mL, 0.5mL, 0.75mL, 1mL of the reference substance stock solution 2 respectively into a 10mL volumetric flask, dilute to the mark with 50% acetonitrile, shake well, and mark them as L-10 , L-50, L-80, L-100, L-150 and L-200. Pipette 0.1 mL of L-100 into a 10 mL volumetric flask, dilute to the mark with 50% acetonitrile, and shake up to make L-1%.

[0061] According to the measurement method provided in Example 1, samples were injected and determ...

Embodiment 3

[0065] The standard addition recovery test of the determination method provided in Example 1.

[0066] The accuracy of the measurement method provided in Example 1 was analyzed by the method of standard addition and recovery.

[0067] Take 10 mg of the new raw material of solitary sodium succinate, accurately weigh it, and place 11 parts in parallel in a 10 mL volumetric flask. Take 2 parts of them and dissolve them with 50% acetonitrile to the mark, mix well, and determine 4 in the sample. -Chloroaniline and (-)-4'-Chloroaniline tartaramic acid content; take 3 of them, add 0.25mL reference substance stock solution 2, dissolve it with 50% acetonitrile to the mark, and mix well, as 50% Add standard recovery solution; take 3 of them, add 0.5mL reference substance stock solution 2, dissolve to the mark with 50% acetonitrile, mix well, as a 100% standard recovery solution; take 3 of them and add 0.7 mL of reference substance stock solution 2, dissolved in 50% acetonitrile to the mark,...

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Abstract

The invention provides a method for determining aniline-type genotoxic impurities in a novel solifenacin succinate crude drug. The method comprises the steps that 4-chloroaniline and (-)-4'-chloroaniline tartramide acid are used as reference substances, a 50% of acetonitrile water solution is used as a solvent, reference substance solutions of the 4-chloroaniline and the (-)-4'-chloroaniline tartramide acid are prepared, the novel solifenacin succinate crude drug is obtain and is dissolved with 50% of acetonitrile water solution to obtain a test solution; detection is performed with a UPLC-MSmethod, the peak areas of the 4-chloroaniline and the (-)-4'-chloroaniline tartramide acid in the reference substance solutions are respectively obtained, and respective response factors are calculated; the test solution is detected by the UPLC-MS method, the peak area of the test solution is obtained, and the content of the 4-chloroaniline and the (-)-4'-chloroaniline tartramide acid in the testsolution is calculated according to the response factors. The method has the advantgaes of being short in detection time, good in accuracy, high in precision and good in repeatability.

Description

Technical field [0001] The invention belongs to the technical field of drug detection for a new sodium succinate raw material drug, and specifically relates to a method for determining aniline genotoxic impurities in a new solide sodium succinate raw material. Background technique [0002] 4-Chloroaniline and (-)-4'-Chloroaniline Tartaramic acid are aniline-type genotoxic impurities. They are widely used as starting materials and intermediates for drug synthesis, but because 4-chloroaniline and (-) -4'-Chloroaniline Tartaramic acid is potentially toxic to cells, so it is necessary to control its content in the drug, but there is currently no quality standard for 4-Chloroaniline and (-)-4'-Chloroaniline Tartaramide Method for determination of acid content. [0003] Therefore, there is an urgent need for a method for the determination of aniline-type genotoxic impurities in new raw materials of sodium succinate with short detection time, good accuracy, high precision and good repeat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/88
CPCG01N30/88G01N2030/045G01N2030/8827
Inventor 嵇慧卿徐红兰顾凯朱子丰
Owner 上海明捷医药科技有限公司
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