A method for detecting the limit of aminoacetonitrile residue

Abstract

The present invention relates to the field of biochemical technology, and discloses a method for detecting the limit of aminoacetonitrile residue. The limit detection method includes the following steps: sample treatment, precisely measuring a control solution and a solution to be tested into a test tube, adding an acetonitrile solution of triethylamine and an acetonitrile solution of phenyl isothiocyanate, mixing well and reacting at 40 °C for 30 min; looking through from top to bottom, comparing the depth of the color of the solutions in the two tubes, so as to determine whether the aminoacetonitrile in the sample to be tested exceeds the limit; the method for detecting the limit of aminoacetonitrile residue of the present invention provides a limit detection method with simple operation, fast and convenient, high accuracy, good repeatability, can determine the limit of the aminoacetonitrile residue amount of the sample to be tested, has great application value in the quality control of drug research and development and production, the method provided by the present invention has high generality, the required instruments, derivatization reagents, etc. are all conventional configurations of most pharmaceutical enterprises and research institutions, and its operation is simple and the cost is low.

Description

Technical Field

[0001] The present invention relates to the field of biochemical technology, and specifically relates to a method for detecting the limit of aminoacetonitrile residue. Background Art

[0002] Aminoacetonitrile, also known as 2-aminoacetonitrile, β-aminoacetonitrile, or glycinonitrile, etc., is mostly stored in the form of hydrochloride, that is, aminoacetonitrile hydrochloride. It is a chemical intermediate and raw material with a relatively large dosage, and is mainly used in the preparation of glycine, ethylenediamine, the new anti-inflammatory drug iguratimod, timolol maleate, the plant regulator thidiazuron, etc., and has a wide range of applications in the fields of pesticides and pharmaceuticals.

[0003] However, the chemical, physical, and toxic properties of aminoacetonitrile have not been fully studied, and its residue in zolamine hydrochloride may affect the safety of drug use. According to the requirements of the "General Principles for the Analysis of Pharmaceutical Impurities 9102" in the Chinese Pharmacopoeia 2020 Edition, aminoacetonitrile belongs to process-related impurities. However, aminoacetonitrile has a very weak ultraviolet absorption peak and lacks a corresponding color development method, resulting in the current research on the detection method for the limit of aminoacetonitrile residue being imperfect and lacking a general detection method for the limit. It has been reported that the content of aminoacetonitrile can be detected by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS), but the equipment required for this method is expensive, and its cost is difficult to bear by most pharmaceutical enterprises and research institutions. Therefore, it is difficult to promote the detection of aminoacetonitrile residue in conventional drug research and development and actual production of enterprises. For this reason, a method for detecting the limit of aminoacetonitrile residue is proposed. Summary of the Invention

[0004] Aiming at the deficiencies of the prior art, the present invention provides a method for detecting the limit of aminoacetonitrile residue, and the limit detection method includes the following steps:

[0005] Step 1: Sample treatment. Precisely measure the control solution and the test solution into a test tube, add a acetonitrile solution of triethylamine and a acetonitrile solution of phenyl isothiocyanate, mix well, and react at 40 °C for 30 min;

[0006] Step 2: Look through from top to bottom, compare the color depth of the solutions in the two tubes, and thus determine whether the aminoacetonitrile in the test sample exceeds the limit.

[0007] Preferably, in step 1, the volume ratio of triethylamine to acetonitrile in the acetonitrile solution of triethylamine is: (0.5 - 1.5):(0.5 - 1.5), and the preferred volume ratio is 1:1.

[0008] Preferably, in step 1, the volume ratio of phenyl isothiocyanate to acetonitrile in the acetonitrile solution of phenyl isothiocyanate is: (0.5 - 1.5):(4.5 - 13.5), and the preferred volume ratio is 1:9.

[0009] Preferably, in step one, the volume ratio of the control solution or the test solution: triethylamine solution: phenyl isothiocyanate solution is (0.5 - 1.5):(0.5 - 1.5):(0.5 - 1.5), and the preferred volume ratio is 1:1:1.

[0010] Preferably, in step one, the reaction time is 20 - 40 min, and the preferred reaction time is 30 min.

[0011] Preferably, in step one, the reaction temperature is 30 - 50 °C, and the preferred reaction temperature is 40 °C.

[0012] Compared with the prior art, the present invention has the following beneficial effects: The limit detection method for aminoacetonitrile residue of the present invention provides a limit detection method that is simple, rapid, convenient, highly accurate, and has good repeatability. It can determine the limit of aminoacetonitrile residue in the test sample, and has great application value in the quality control of drug research and development and production. The method provided by the present invention has high versatility, and the required instruments, derivatization reagents, etc. are all routinely configured by most pharmaceutical enterprises and research institutions. Its operation is simple and the cost is low. Specific Embodiments

[0013] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0014] A limit detection method for aminoacetonitrile residue, the limit detection method comprising the following steps:

[0015] Step one, sample treatment: accurately measure the control solution and the test solution into a test tube, add the acetonitrile solution of triethylamine and the acetonitrile solution of phenyl isothiocyanate, mix well and react at 40 °C for 30 min;

[0016] Step two, view from top to bottom, compare the color depth of the solutions in the two tubes, so as to judge whether the aminoacetonitrile in the test sample exceeds the limit.

[0017] Among them, in step one, the volume ratio of triethylamine to acetonitrile in the acetonitrile solution of triethylamine is: (0.5 - 1.5):(0.5 - 1.5), and the preferred volume ratio is 1:1.

[0018] Among them, in step one, the volume ratio of phenyl isothiocyanate to acetonitrile in the acetonitrile solution of phenyl isothiocyanate is: (0.5 - 1.5):(4.5 - 13.5), and the preferred volume ratio is 1:9.

[0019] Among them, in step one, the volume ratio of the reference solution or the test solution: triethylamine solution: phenyl isothiocyanate solution is (0.5 - 1.5):(0.5 - 1.5):(0.5 - 1.5), and the preferred volume ratio is 1:1:1.

[0020] Among them, in step one, the reaction time is 20 - 40 min, and the preferred reaction time is 30 min.

[0021] Among them, in step one, the reaction temperature is 30 - 50 °C, and the preferred reaction temperature is 40 °C.

[0022] It should be noted that: the limit detection method for aminoacetonitrile residue in the present invention provides a limit detection method with simple operation, fast and convenient, high accuracy, and good repeatability. It can determine the limit of the aminoacetonitrile residue in the test sample, and has great application value in the quality control of drug research and development and production. The method provided by the present invention has high generality, and the required instruments, derivatization reagents, etc. are all conventional configurations of most pharmaceutical enterprises and research institutions. Its operation is simple and the cost is low, which is suitable for large-scale promotion and use;

[0023] The content not described in detail in this specification belongs to the prior art well-known to those skilled in the art.

[0024] Example

[0025] Limit detection of aminoacetonitrile residue in amines hydrochloride

[0026] Preparation of reference solution: Take an appropriate amount of aminoacetonitrile hydrochloride (about 50 mg of aminoacetonitrile), accurately weigh it, place it in a 10 ml volumetric flask, dissolve it with water and dilute to the mark, shake well, then accurately measure 1 ml and place it in a 100 ml volumetric flask, dissolve it with water and dilute to the mark, shake well.

[0027] Preparation of test solution: Take an appropriate amount of amines hydrochloride, accurately weigh it, dissolve it with water and quantitatively dilute it to a solution containing about 50 mg per 1 ml.

[0028] Preparation of acetonitrile solution of triethylamine: Take 5 ml of triethylamine, add acetonitrile to make 10 ml, and you will get it.

[0029] Preparation of acetonitrile solution of phenyl isothiocyanate: Take 1 ml of phenyl isothiocyanate, add acetonitrile to make 10 ml, and you will get it.

[0030] Derivatization treatment of reference solution and test solution: Take 2 ml of the test solution, add 2 ml of the acetonitrile solution of triethylamine, add 2 ml of the acetonitrile solution of phenyl isothiocyanate as tube B; take 2 ml of the reference solution and operate in the same way as tube A. Place tubes A and B at 40 °C for 30 min.

[0031] Test result: Looking at the two tubes of A and B from top to bottom in the previous step, the color shown in tube B is lighter than that in tube A (<0.1%);

[0032] In summary, the analysis method for aminoacetonitrile residue provided by the present invention has high accuracy and good operability, and can be widely applied to the analysis and detection of aminoacetonitrile residue.

[0033] It should be noted that in this article, relational terms such as first and second are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the term "comprising", "including" or any other variant thereof is intended to cover non-exclusive inclusion, so that a process, method, article or device comprising a series of elements not only includes those elements, but also includes other elements not expressly listed, or further includes elements inherent to such process, method, article or device.

[0034] Although the embodiments of the present invention have been shown and described, those of ordinary skill in the art can understand that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for detecting the limit of aminoacetonitrile residue, characterized in that, This limit detection method includes the following steps: Step 1: Sample treatment. Precisely measure the reference solution and the test solution into test tubes respectively, add the acetonitrile solution of triethylamine and the acetonitrile solution of phenyl isothiocyanate, mix well, and react at 40 °C for 30 min; Step 2: View from top to bottom and compare the color depth of the solutions in the two tubes to determine whether the aminoacetonitrile in the test sample exceeds the limit.

2. The limit detection method for aminoacetonitrile residue according to claim 1, wherein: In the acetonitrile solution of triethylamine in Step 1, the volume ratio of triethylamine to acetonitrile is (0.5 - 1.5):(0.5 - 1.5).

3. The limit detection method for aminoacetonitrile residue according to claim 1, wherein: In the acetonitrile solution of triethylamine in Step 1, the volume ratio of triethylamine to acetonitrile is 1:

1.

4. The limit detection method for aminoacetonitrile residue according to claim 1, characterized in that: In the acetonitrile solution of phenyl isothiocyanate in Step 1, the volume ratio of phenyl isothiocyanate to acetonitrile is (0.5 - 1.5):(4.5 - 13.5).

5. The limit detection method for aminoacetonitrile residue according to claim 1, wherein: In the acetonitrile solution of phenyl isothiocyanate in Step 1, the volume ratio of phenyl isothiocyanate to acetonitrile is 1:

9.

6. The limit detection method for aminoacetonitrile residue according to claim 1, wherein: In Step 1, the volume ratio of the reference solution or the test solution: the acetonitrile solution of triethylamine: the acetonitrile solution of phenyl isothiocyanate is (0.5 - 1.5):(0.5 - 1.5):(0.5 - 1.5).

7. The limit detection method for aminoacetonitrile residue according to claim 1, characterized in that: In Step 1, the volume ratio of the reference solution or the test solution: the acetonitrile solution of triethylamine: the acetonitrile solution of phenyl isothiocyanate is 1:1:1.