Method for detecting chloride in aminoheterocyclic drug

Abstract

The application provides a method for detecting chloride in an aminoheterocyclic drug, characterized in that, before detection, the aminoheterocyclic drug is pretreated. The detection method of the application is beneficial to exclude detection interference, and has the advantages of high detection accuracy, high detection sensitivity, simple operation, time and cost saving, and the like.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a method for detecting chlorides in ammonia-containing heterocyclic drugs. Background Technology

[0002] Detecting and monitoring chloride residues in drugs is an important indicator of drug quality control. The Chloride Test Method (General Determination 0801) in the Chinese Pharmacopoeia (2015 Edition) (hereinafter referred to as the Ch.P 2015 General Method) utilizes the reaction of chloride with silver nitrate test solution in acidic nitric acid solution to produce a white turbid liquid of silver chloride. This is then compared with the silver chloride turbid liquid produced by a certain amount of sodium chloride standard solution under the same conditions. By comparing the turbidity or the degree of turbidity visible to the naked eye, it can be determined whether the chloride in the test sample exceeds the limit.

[0003] The general method according to Ch.P 2015 includes the following steps: Unless otherwise specified, take the specified amount of the test sample under each variety, dissolve it in water to make 25 ml (if the solution is alkaline, add nitric acid to make it neutral), then add 10 ml of dilute nitric acid; if the solution is not clear, filter it; place the solution in a 50 ml Nessler tube, add water to make about 40 ml, and shake well to obtain the test solution. Separately, take the specified amount of standard sodium chloride solution under the same variety, place it in a 50 ml Nessler tube, add 10 ml of dilute nitric acid, add water to make 40 ml, and shake well to obtain the control solution. Add 1.0 ml of silver nitrate test solution to both the test solution and the control solution, dilute with water to make 50 ml, shake well, and place in the dark for 5 minutes. Place them on a black background and observe from above the colorimetric tubes, comparing the turbidity or the depth of turbidity.

[0004] However, the Ch.P 2015 general method is not applicable to the detection of chloride residues in all drugs. When the test solution is colored, color interference needs to be eliminated. When using the Ch.P 2015 general method to detect chloride in ammonia-containing heterocyclic drugs, the reaction between the active pharmaceutical ingredient and silver nitrate may interfere with the detection results and result interpretation.

[0005] When interference exists in the sample being tested, methods such as ion chromatography and oxygen flask combustion are commonly used to eliminate the interference from the sample in chloride detection. However, ion chromatography requires large, expensive instruments and demands high levels of skill from technicians, high-quality consumables, and high reagent purity, and is also time-consuming, labor-intensive, and costly. Oxygen flask combustion requires oxygen for combustion, which can easily lead to explosions, resulting in high risks, cumbersome operation, time consumption, low sensitivity, and high cost. Therefore, there is an urgent need to develop an effective method to eliminate the interference of ammonia-containing heterocyclic drugs in chloride detection. Summary of the Invention

[0006] This invention provides a method for detecting chlorides in ammonia-containing heterocyclic drugs, characterized in that the ammonia-containing heterocyclic drugs are pretreated before detection.

[0007] In a preferred embodiment of the present invention, the pretreatment includes the following steps: acidifying the ammonia-containing heterocyclic drug with an acidifying reagent, extracting with an organic solvent, and taking the lower layer solution after extraction for detection. The acidifying reagent excludes any one or a combination of HCl, HBr, HI, HF, C2HF3O2 (trifluoroacetic acid), H2CO3, H2SO4 (sulfuric acid), H3PO4 (phosphoric acid), H3BO3 (boric acid), and CH3COOH (acetic acid). The organic solvent excludes any one or a combination of methanol, ethanol, isopropanol, acetone, and halogenated hydrocarbons.

[0008] In a preferred embodiment of the present invention, the amino-containing heterocyclic drug is a valsartan-containing drug, preferably sacubitril / valsartan sodium.

[0009] In a preferred embodiment of the present invention, the acidifying agent is a nitric acid solution.

[0010] In a preferred embodiment of the present invention, the concentration of the acidifying agent is 2.5%-69%, preferably 5.0%-40%, and more preferably 9.5%-12.5%.

[0011] In a preferred embodiment of the present invention, the organic solvent is selected from any one or a combination of esters, ethers, alkanes.

[0012] In a preferred embodiment of the present invention, the organic solvent is selected from any one or a combination of ethyl acetate, methyl acetate, diethyl ether, isopropyl ether, petroleum ether, n-heptane, and n-hexane.

[0013] In a preferred embodiment of the present invention, the pretreatment of the ammonia-containing heterocyclic drug includes the following steps: taking the ammonia-containing heterocyclic drug, dissolving it in water, adding an acidifying reagent for acidification, then adding an organic solvent for extraction, and taking the lower layer solution after extraction for detection.

[0014] In a preferred embodiment of the present invention, the number of extractions is 1-5 times, preferably 2-4 times.

[0015] In a preferred embodiment of the present invention, the concentration of the aqueous solution containing the ammonia heterocyclic drug is ≤0.25g / ml, preferably 0.015g / ml-0.20g / ml, and more preferably 0.02g / ml-0.15g / ml.

[0016] In a preferred embodiment of the present invention, the molar ratio of the ammonia-containing heterocyclic drug to the acidifying reagent is 1:12-63, preferably 1:20-40, and more preferably 1:31-36.

[0017] In a preferred embodiment of the present invention, the mass-to-volume ratio (g / ml) of the ammonia-containing heterocyclic drug to the organic solvent is 0.25:20-100; preferably 0.25:40-60, and more preferably 0.25:50-55.

[0018] In a preferred embodiment of the present invention, the pretreatment of the ammonia-containing heterocyclic drug includes the following steps: take 0.25g of the ammonia-containing heterocyclic drug, add 15ml of water to dissolve it, add 5ml of dilute nitric acid with a concentration of 9.5%-10.5% for acidification, then add 50ml of ethyl acetate for extraction, and take the lower layer solution for detection.

[0019] In a preferred embodiment of the present invention, the extraction is performed 1-5 times, preferably 2-3 times.

[0020] In a preferred embodiment of the present invention, the lower layer solution after extraction is tested according to the general method of Ch.P 2015.

[0021] In a preferred embodiment of the present invention, the step of taking the lower layer solution after extraction and detecting it according to the general method of Ch.P 2015 includes the following steps:

[0022] 1) Preparation of test solution: Place the lower layer solution after extraction in a colorimetric tube, add 10 ml of dilute nitric acid, add water to make up to 40 ml, and shake well for later use;

[0023] 2) Preparation of control solution: Take 5 ml of standard sodium chloride solution, place it in a colorimetric tube, add 10 ml of dilute nitric acid, add water to make up to 40 ml, shake well and set aside.

[0024] 3) Add 1 ml of 0.1 mol / L silver nitrate solution to the test solution and the control solution respectively, add water to dilute to 50 ml, shake well, place in the dark for 5 minutes, place on a black background, observe from above the colorimetric tube, and compare the color or turbidity of the two solutions or a combination thereof to obtain the result.

[0025] In a preferred embodiment of the present invention, the concentration of the dilute nitric acid solution is 2.5%-69%, preferably 5.0%-40%, and more preferably 9.5%-12.5%.

[0026] Another object of the present invention is to provide a method for detecting chloride in a drug containing valsartan, characterized in that the drug containing valsartan is pretreated before detection.

[0027] In a preferred embodiment of the present invention, the pretreatment includes the following steps: acidifying the drug containing valsartan with an acidifying reagent, extracting with an organic solvent, and taking the lower layer solution after extraction for detection. The acidifying reagent excludes any one or a combination of HCl, HBr, HI, HF, C2HF3O2 (trifluoroacetic acid), H2CO3, H2SO4 (sulfuric acid), H3PO4 (phosphoric acid), H3BO3 (boric acid), and CH3COOH (acetic acid). The organic solvent excludes any one or a combination of methanol, ethanol, isopropanol, acetone, and halogenated hydrocarbons.

[0028] In a preferred embodiment of the present invention, the valsartan-containing drug is sacubitril / valsartan sodium.

[0029] In a preferred embodiment of the present invention, the acidifying agent is a nitric acid solution.

[0030] In a preferred embodiment of the present invention, the concentration of the acidifying agent is 2.5%-69%, preferably 5.0%-40%, and more preferably 9.5%-12.5%.

[0031] In a preferred embodiment of the present invention, the organic solvent is selected from any one or a combination of esters, ethers, alkanes.

[0032] In a preferred embodiment of the present invention, the organic solvent is selected from any one or a combination of ethyl acetate, methyl acetate, diethyl ether, isopropyl ether, petroleum ether, n-heptane, and n-hexane.

[0033] In a preferred embodiment of the present invention, the pretreatment of the drug containing valsartan includes the following steps: taking the drug containing valsartan, dissolving it in water, adding an acidifying reagent for acidification, then adding an organic solvent for extraction, and taking the lower layer solution after extraction for detection.

[0034] In a preferred embodiment of the present invention, the number of extractions is 1-5 times, preferably 2-4 times.

[0035] In a preferred embodiment of the present invention, the concentration of the aqueous solution containing valsartan is ≤0.25g / ml, preferably 0.015g / ml-0.20g / ml, and more preferably 0.02g / ml-0.15g / ml.

[0036] In a preferred embodiment of the present invention, the molar ratio of the drug containing valsartan to the acidifying agent is 1:12-63, preferably 1:20-40, and more preferably 1:31-36.

[0037] In a preferred embodiment of the present invention, the mass-volume ratio (g / ml) of the drug containing valsartan to the organic solvent is 0.25:20-100; preferably 0.25:40-60, and more preferably 0.25:50-55.

[0038] In a preferred embodiment of the present invention, the drug pretreatment containing valsartan includes the following steps: take 0.25g of an amino-containing heterocyclic drug, add 15ml of water to dissolve it, add 5ml of dilute nitric acid with a concentration of 9.5%-10.5% for acidification, then add 50ml of ethyl acetate for extraction, and take the lower layer solution for detection.

[0039] In a preferred embodiment of the present invention, the extraction is performed 1-5 times, preferably 2-3 times.

[0040] In a preferred embodiment of the present invention, the lower layer solution after extraction is tested according to the general method of Ch.P 2015.

[0041] In a preferred embodiment of the present invention, the step of taking the lower layer solution after extraction and detecting it according to the general method of Ch.P 2015 includes the following steps:

[0042] 1) Preparation of test solution: Place the lower layer solution after extraction in a colorimetric tube, add 10 ml of dilute nitric acid, add water to make up to 40 ml, and shake well for later use;

[0043] 2) Preparation of control solution: Take 5 ml of standard sodium chloride solution, place it in a colorimetric tube, add 10 ml of dilute nitric acid, add water to make up to 40 ml, shake well and set aside.

[0044] 3) Add 1 ml of 0.1 mol / L silver nitrate solution to the test solution and the control solution respectively, add water to dilute to 50 ml, shake well, place in the dark for 5 minutes, place on a black background, observe from above the colorimetric tube, and compare the color or turbidity of the two solutions or a combination thereof to obtain the result.

[0045] In a preferred embodiment of the present invention, the concentration of the dilute nitric acid solution is 2.5%-69%, preferably 5.0%-40%, and more preferably 9.5%-12.5%.

[0046] Another object of the present invention is to provide a method for detecting chloride in sacubitril / valsartan sodium, characterized in that the sacubitril / valsartan sodium is pretreated before detection.

[0047] In a preferred embodiment of the present invention, the pretreatment includes the following steps: acidifying sacubitril / valsartan sodium with an acidifying reagent, extracting with an organic solvent, and taking the lower layer solution after extraction for detection. The acidifying reagent excludes any one or a combination of HCl, HBr, HI, HF, C2HF3O2 (trifluoroacetic acid), H2CO3, H2SO4 (sulfuric acid), H3PO4 (phosphoric acid), H3BO3 (boric acid), and CH3COOH (acetic acid). The organic solvent excludes any one or a combination of methanol, ethanol, isopropanol, acetone, and halogenated hydrocarbons.

[0048] In a preferred embodiment of the present invention, the acidifying agent is a nitric acid solution.

[0049] In a preferred embodiment of the present invention, the concentration of the acidifying agent is 2.5%-69%, preferably 5.0%-40%, and more preferably 9.5%-12.5%.

[0050] In a preferred embodiment of the present invention, the organic solvent is selected from any one or a combination of esters, ethers, alkanes.

[0051] In a preferred embodiment of the present invention, the organic solvent is selected from any one or a combination of ethyl acetate, methyl acetate, diethyl ether, isopropyl ether, petroleum ether, n-heptane, and n-hexane.

[0052] In a preferred embodiment of the present invention, the pretreatment of sacubitril / valsartan sodium includes the following steps: taking sacubitril / valsartan sodium, dissolving it in water, adding an acidifying reagent for acidification, then adding an organic solvent for extraction, and taking the lower layer solution after extraction for detection.

[0053] In a preferred embodiment of the present invention, the number of extractions is 1-5 times, preferably 2-4 times.

[0054] In a preferred embodiment of the present invention, the concentration of the sacubitril / valsartan sodium aqueous solution is ≤0.25g / ml, preferably 0.015g / ml-0.20g / ml, and more preferably 0.02g / ml-0.15g / ml.

[0055] In a preferred embodiment of the present invention, the molar ratio of sacubitril / valsartan sodium to the acidifying agent is 1:12-63, preferably 1:20-40, and more preferably 1:31-36.

[0056] In a preferred embodiment of the present invention, the mass-volume ratio (g / ml) of sacubitril / valsartan sodium to organic solvent is 0.25:20-100; preferably 0.25:40-60, and more preferably 0.25:50-55.

[0057] In a preferred embodiment of the present invention, the pretreatment of sacubitril / valsartan sodium includes the following steps: take 0.25g of sacubitril / valsartan sodium, add 15ml of water to dissolve it, add 5ml of dilute nitric acid with a concentration of 9.5%-10.5% for acidification, then add 50ml of ethyl acetate for extraction, and take the lower layer solution for detection.

[0058] In a preferred embodiment of the present invention, the extraction is performed 1-5 times, preferably 2-3 times.

[0059] In a preferred embodiment of the present invention, the lower layer solution after extraction is tested according to the general method of Ch.P 2015.

[0060] In a preferred embodiment of the present invention, the step of taking the lower layer solution after extraction and detecting it according to the general method of Ch.P 2015 includes the following steps:

[0061] 1) Preparation of test solution: Place the lower layer solution after extraction in a colorimetric tube, add 10 ml of dilute nitric acid, add water to make up to 40 ml, and shake well for later use;

[0062] 2) Preparation of control solution: Take 5 ml of standard sodium chloride solution, place it in a colorimetric tube, add 10 ml of dilute nitric acid, add water to make up to 40 ml, shake well and set aside.

[0063] 3) Add 1 ml of 0.1 mol / L silver nitrate solution to the test solution and the control solution respectively, add water to dilute to 50 ml, shake well, place in the dark for 5 minutes, place on a black background, observe from above the colorimetric tube, and compare the color or turbidity of the two solutions or a combination thereof to obtain the result.

[0064] In a preferred embodiment of the present invention, the concentration of the dilute nitric acid solution is 2.5%-69%, preferably 5.0%-40%, and more preferably 9.5%-12.5%.

[0065] Unless otherwise stated, when this invention relates to percentages between liquids, the percentage is volume / volume percentage; when this invention relates to percentages between liquids and solids, the percentage is volume / weight percentage; when this invention relates to percentages between solids and liquids, the percentage is weight / volume percentage; the remainder is weight / weight percentage.

[0066] Compared with the prior art, the present invention has the following beneficial technical effects:

[0067] This invention provides a simple method for detecting chloride residues in ammonia-containing heterocyclic drugs by exploring and optimizing the pretreatment conditions of the test samples. This method helps to eliminate detection interference, facilitates more efficient drug quality control, and has the advantages of high detection accuracy, high detection sensitivity, simple operation, and saving time and cost. Attached Figure Description

[0068] Figure 1-1 The detection results of Experiment Example 1: Test sample (top) - Control sample (bottom left) - Recovery rate (bottom right)

[0069] Figure 1-2 The detection results of Example 1, test sample - control sample - recovery rate Detailed Implementation

[0070] The following description of specific embodiments of the present invention does not limit the present invention. Those skilled in the art can make various changes or modifications based on the present invention, and as long as they do not depart from the spirit of the present invention, they should all fall within the scope of protection of the claims of the present invention.

[0071] Comparative Example 1

[0072] Dissolve 0.5g of sacubitril / valsartan sodium in 20ml of water, add 20ml of dilute nitric acid, and dilute to 50ml with water. Shake well; a flocculent precipitate forms. Filter the solution, and transfer 25ml of the filtrate to a 50ml Nessler tube. Add water to make approximately 40ml and shake well. This is the test solution. Add 1.0ml of silver nitrate solution (0.1mol / L). A large amount of milky white precipitate immediately appears. After heating in a water bath, the milky white color disappears, and the solution returns to its milky white color after cooling.

[0073] The results indicate that the sample interferes with the detection of chloride ions, and this method is not suitable for the detection of sacubitril / valsartan sodium chloride.

[0074] Comparative Example 2

[0075] Sacubitril calcium: Dissolve 0.5g of sacubitril calcium in 20ml of water, add 20ml of dilute nitric acid, and dilute to 50ml with water. A flocculent precipitate will form. Shake well, filter, and transfer 25ml of the filtrate to a 50ml Nessler tube. Dilute with water to 40ml, shake well, and use this as the test solution. Add 1.0ml of silver nitrate solution (0.1mol / L). The solution will become clear and colorless.

[0076] Valsartan: Take 0.5g of valsartan, add 40ml of water (the sample is insoluble), sonicate for 10 minutes, add water to make up to 50ml, shake well, and filter. Take 25ml of the filtrate and place it in a 50ml Nessler tube. Add 10ml of dilute nitric acid, add water to make 40ml, shake well, and use this as the test solution. Add 1.0ml of silver nitrate test solution (concentration 0.1mol / L), and a large amount of milky white precipitate immediately appears. The milky white color disappears after heating in a water bath. The solution returns to milky white after cooling.

[0077] Valsartan interferes with the detection of chloride ions in sacubitril and valsartan sodium.

[0078] Comparative Examples 3-6

[0079] The detection solvent in the Ch.P 2015 general method was changed from water to other solvents. The results are shown in Table 1.

[0080] Table 1

[0081]

[0082] Comparative Examples 7-9

[0083] 1. Pretreatment of the test solution sample:

[0084] 1) Dissolution: Take 0.25g of sacubitril / valsartan sodium in a separatory funnel and add water to dissolve it;

[0085] 2) Acidification: Add an acidifying agent;

[0086] 3) Extraction: Add organic solvent, shake vigorously to mix, let stand, and take the lower layer solution.

[0087] 2. Pretreatment of recovery solution samples:

[0088] 1) Dissolution: Take 0.25g of sacubitril / valsartan sodium into a separatory funnel, add 5ml of standard sodium chloride solution, and add water to dissolve;

[0089] 2) Acidification: Add an acidifying agent;

[0090] 3) Extraction: Add organic solvent, shake vigorously to mix, let stand, and take the lower layer solution.

[0091] 2. The Ch.P 2015 general method was used for detection.

[0092] 1) Preparation of test solution and recovery solution: Take the lower layer solution obtained after pretreatment into a 50ml Nessler tube, add 10ml of 10% dilute nitric acid, add water to make 40ml, shake well and set aside.

[0093] Preparation of control solution: Take 5 ml of standard sodium chloride solution, place it in a 50 ml Nessler tube, add 10 ml of 10% dilute nitric acid, add water to make 40 ml, shake well, and set aside.

[0094] 2) Add 1 ml of silver nitrate solution (concentration 0.1 mol / L) to the test solution, recovery solution, and control solution respectively, dilute with water to make 50 ml, shake well, place in the dark for 5 minutes, place on a black background, and observe and compare from above. The results are shown in Table 2.

[0095] Table 2

[0096]

[0097] Comparative Example 10

[0098] 1. Pretreatment of the test solution sample:

[0099] Take 2g of anhydrous sodium carbonate and spread it on the bottom and sides of a crucible. Then take 0.5g of sacubitril / valsartan sodium and place it on top of the anhydrous sodium carbonate. Moisten with 1ml of water. After drying, first ignite it over a low flame to carbonize it, then ignite it at 700-800℃ to completely ashed it. Let it cool, add an appropriate amount of water to dissolve it, filter it, wash the crucible and filter with water, combine the filtrate and washings, place them in a 50ml volumetric flask, dilute with water to the mark, shake well, accurately measure 10ml, place it in a 50ml Nessler tube, and add water to make 25ml. Set aside.

[0100] 2. Pretreatment of recovery solution samples:

[0101] Take 2g of anhydrous sodium carbonate and spread it on the bottom and sides of a crucible. Then take 0.5g of sacubitril / valsartan sodium and place it on top of the anhydrous sodium carbonate. Moisten with 1ml of a standard sodium chloride solution with a concentration of 5 times the concentration. After drying, first ignite it over a low flame to carbonize it, then ignite it at 700-800℃ to completely ashed it. Let it cool, add an appropriate amount of water to dissolve it, filter it, wash the crucible and filter with water, combine the filtrate and washings, place them in a 50ml volumetric flask, dilute with water to the mark, shake well, accurately measure 10ml, place it in a 50ml Nessler tube, and add water to make 25ml. Set aside.

[0102] 3. Detection was performed using the Ch.P 2015 general method.

[0103] Preparation of test solution and recovery solution: Take the pretreated solution, add 10 ml of 9.5% dilute nitric acid, add water to make about 40 ml, and shake well. Set aside.

[0104] Preparation of the control solution: Take 5 ml of standard sodium chloride solution and place it in a 50 ml Nessler tube. Add 10 ml of 9.5% dilute nitric acid and dilute with water to make 40 ml. Shake well to obtain the control solution. Set aside for later use.

[0105] Add 1 ml of silver nitrate solution (concentration of 0.1 mol / L) to the test solution, recovery solution and control solution respectively, dilute with water to make 50 ml, shake well, place in the dark for 5 minutes, place on a black background and observe and compare from above the colorimetric tube.

[0106] Comparison of turbidity levels: Test solution < Recovery solution < Control solution. Chloride ions cannot be accurately measured.

[0107] Example 1

[0108] The method for detecting chloride in sacubitril / valsartan sodium includes the following steps:

[0109] 1. Pretreatment of the test solution sample:

[0110] 1) Dissolution: Take 0.25g of sacubitril / valsartan sodium, place it in a separatory funnel, and add 15ml of water to dissolve it;

[0111] 2) Acidification: Add 5 ml of dilute nitric acid (concentration 10.5%);

[0112] 3) Extraction: Add 50 ml of ethyl acetate, shake vigorously to mix, let stand, and take the lower layer solution;

[0113] 4) Repeat extraction: Add 50 ml of ethyl acetate to the lower layer solution obtained in step 3), shake vigorously to mix, let stand, and take the lower layer solution.

[0114] 2. Pretreatment of recovery solution samples:

[0115] 1) Dissolution: Take 0.25g of sacubitril / valsartan sodium, place it in a separatory funnel, add 5ml of standard sodium chloride solution and 10ml of water to dissolve it;

[0116] 2) Acidification: Add 5 ml of dilute nitric acid;

[0117] 3) Extraction: Add 50 ml of ethyl acetate, shake vigorously to mix, let stand, and take the lower layer solution;

[0118] 4) Repeat extraction: Add 50 ml of ethyl acetate to the lower layer solution obtained in step 3), shake vigorously to mix, let stand, and take the lower layer solution.

[0119] 3. Detection was performed using the Ch.P 2015 general method:

[0120] 1) Solution preparation

[0121] Preparation of test solution and recovery solution: Take the lower layer solution obtained after pretreatment into a Nessler tube, add 10 ml of dilute nitric acid (concentration of 10.5%), add water to make 40 ml, and shake well for later use.

[0122] Preparation of control solution: Take 5 ml of standard sodium chloride solution, place it in a Nessler tube, add 10 ml of dilute nitric acid (concentration of 10.5%), add water to make 40 ml, and shake well for later use.

[0123] 2) Add 1 ml of silver nitrate solution (concentration of 0.1 mol / L) to the test solution, recovery solution and control solution respectively, dilute with water to 50 ml, shake well, place in the dark for 5 minutes, place on a black background and observe and compare from above the colorimetric tube.

[0124] Comparison of turbidity levels: Test solution < Recovery solution ≤ Control solution. This method can accurately determine chloride ions in sacubitril / valsartan sodium.

[0125] The above description of specific embodiments of the present invention does not limit the present invention. Those skilled in the art can make various changes or modifications based on the present invention, and as long as they do not depart from the spirit of the present invention, they should all fall within the scope of protection of the claims of the present invention.

Claims

1. A method for detecting chloride in an aminoheterocyclic drug, characterized by, The amine-containing heterocyclic drug is a drug containing valsartan. Before detection, the amine-containing heterocyclic drug is pretreated, and the pretreatment comprises the following steps: taking the amine-containing heterocyclic drug, dissolving it in water, acidifying and treating it with a dilute nitric acid solution of an acidifying agent, adding ethyl acetate for extraction, and taking the lower layer solution after extraction for detection. The extraction is performed 2-4 times.

2. The detection method according to claim 1, wherein the amine-containing heterocyclic drug is sacubitril valsartan sodium.

3. The detection method according to claim 2, wherein the concentration of the amine-containing heterocyclic drug aqueous solution is 0.015 g / ml-0.20 g / ml.

4. The detection method according to claim 3, wherein the molar ratio of the amine-containing heterocyclic drug to the acidifying agent is 1:12-63.

5. The detection method according to claim 4, wherein the mass-volume ratio of the amine-containing heterocyclic drug to ethyl acetate is 0.25:40-60 g / ml.

6. The detection method according to claim 5, wherein the pretreatment of the amine-containing heterocyclic drug comprises the following steps: taking 0.25 g of the amine-containing heterocyclic drug, dissolving it in 15 ml of water, adding 5 ml of dilute nitric acid with a concentration of 9.5%-10.5% for acidification treatment, and then adding 50 ml of ethyl acetate for extraction, and taking the lower layer solution for detection.

7. The detection method according to claim 6, wherein the lower layer solution after extraction is detected according to the general method of Ch.P 2015, comprising the following steps: 1) Preparation of test solution: placing the lower layer solution after extraction in a colorimetric tube, adding 10 ml of dilute nitric acid, diluting to 40 ml with water, and shaking well for standby; 2) Preparation of control solution: taking 5 ml of standard sodium chloride solution, placing it in a colorimetric tube, adding 10 ml of dilute nitric acid, diluting to 40 ml with water, and shaking well for standby; 3) Adding 1 ml of silver nitrate solution with a concentration of 0.1 mol / L to the test solution and the control solution, respectively, diluting with water to 50 ml, shaking well, placing in the dark for 5 minutes, observing from the top of the colorimetric tube to the bottom on a black background, and comparing the color or turbidity of either one or a combination thereof, and then obtaining the result.

8. The detection method according to claim 7, wherein the concentration of the dilute nitric acid in steps 1) and 2) is 9.5%-12.5%.

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