Melsartan potassium photodegradation impurity and preparation method thereof

Abstract

The invention belongs to the field of biological medicine, and particularly relates to a Milsartan potassium photodegradation impurity and a preparation method thereof. The method comprises the following steps: carrying out illumination destruction on Milsartan potassium powder under the condition of contacting with air, enriching with an organic solvent, carrying out column chromatography separation and recrystallization purification to obtain the novel Milsartan potassium photodegradation impurity, and the highest purity of the obtained impurity is 99.6%. The photodegradation impurity disclosed by the invention is actually detected in related substance inspection of a photostability test of a Milsartan potassium raw material medicine and a Milsartan potassium preparation, the detection values are respectively 0.23% and 0.25%, and the photodegradation impurity is one of main degradation impurities and has research necessity; the structure of the impurity compound is represented, and the impurity compound can be used as an impurity reference substance and is used for analysis, detection, quality control and the like of Milsartan potassium bulk drugs and preparations.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and specifically relates to a photodegradable impurity of asartan potassium and a preparation method thereof. Background Art

[0002] Azilsartan Potassium Tablets are angiotensin II receptor antagonists (ARBs) developed by Takeda Pharmaceutical Company Limited of Japan. They are ester prodrugs of azilsartan and are mainly used to treat hypertension in adults. In January 2021, Azilsartan Potassium Tablets were approved for marketing by NMPA. The structural formula of its active ingredient is shown below:

[0003]

[0004] Impurities are an important research topic for APIs and preparations, and are related to the quality control and safety of drugs. Degradation of APIs and preparations during storage is one of the main ways to produce impurities. To study the degradation of APIs and preparations during storage, strong tests of factors such as acid, alkali, high temperature, oxidation, and light can be set up in stability tests to determine degradation impurities and their degradation pathways. However, different substances have different degradation conditions, and it is impossible to predict under what conditions degradation impurities will be produced. In addition, there is no reference method for how to obtain high-purity impurities.

[0005] As a prodrug, azilsartan potassium tablets are mainly degraded into azilsartan during storage. Currently, there are relatively few studies specifically on the photodegradation of azilsartan potassium raw materials and preparations. It is of great significance to fully study the photodegradation impurities of azilsartan potassium raw materials and preparations. Summary of the invention

[0006] The object of the present invention is to provide a photodegradable impurity of Asartan potassium, the structural formula of which is shown in Formula 1.

[0007]

[0008] Under light conditions, the potassium azesartan reacts with moisture in the air to hydrolyze into azilsartan medoxomil, and under the continued action of light and air moisture, the ester group decomposes and finally stabilizes to a compound of formula I, and the reaction formula is shown below. The present invention also provides a method for preparing an impurity of formula I, wherein a potassium azesartan sample is destroyed by light and then enriched with an organic solvent, separated by column chromatography, and purified by recrystallization to obtain a potassium azesartan photodegradable impurity compound of formula I.

[0009]

[0010] It is worth noting that the compound of formula I was actually detected in the inspection of related substances in the photostability test of the raw materials and preparations of Asartan Potassium, and is one of the main degradation impurities, which is necessary to study. Among them, the related substances of photodegradation impurities in the raw materials of Asartan Potassium are 0.23%, and the related substances of photodegradation impurities in the light damage test of Asartan Potassium preparations are 0.25%.

[0011] The method for preparing the photodegradable impurities of the formula I mesartan potassium provided by the present invention comprises the following steps:

[0012] (1) subjecting the potassium permanganate powder to light destruction in contact with air;

[0013] (2) adding an organic solvent to the light-destructed product obtained in step (1), stirring, filtering, collecting the filtrate, and concentrating to obtain a photodegradable impurity-enriched product;

[0014] (3) separating and purifying the photodegradation impurity enriched product obtained in step (2) by column chromatography, and collecting the elution liquid containing the target product;

[0015] (4) Concentrating the eluted effluent obtained in step (3), adding an organic solvent, heating and stirring until dissolved and clarified, then cooling and crystallizing, filtering and drying to obtain the photodegradable impurity compound of potassium asartan represented by formula I.

[0016] Preferably, the potassium bissartan powder described in step (1) refers to potassium bissartan powder obtained by grinding.

[0017] Preferably, the contact with air condition in step (1) refers to contact of the potassium permanganate powder with air.

[0018] Preferably, the light destruction in step (1) refers to spreading the powder evenly on a culture dish and then placing it in a UV light box for illumination.

[0019] Preferably, the illumination intensity in step (1) is 3000-6000 Lx, and the illumination duration is 16-60 h; more preferably, the illumination duration is 40-60 h.

[0020] Preferably, the organic solvent in step (2) is at least one of tetrahydrofuran, acetone, ethyl acetate and dichloromethane; more preferably, the organic solvent is at least one of tetrahydrofuran / acetone.

[0021] Preferably, the column chromatography filler in step (3) is 200-300 mesh or 300-400 mesh silica gel.

[0022] Preferably, the column chromatography eluent in step (3) is dichloromethane and anhydrous methanol in a volume ratio of 20:1 to 8:1; more preferably, the volume ratio is 20:1 to 15:1.

[0023] Preferably, the organic solvent in step (4) is at least one of dichloromethane, methanol, ethanol and acetone.

[0024] Preferably, the heating temperature in step (4) is 30-60°C, and the cooling and crystallization temperature is 0-20°C.

[0025] In a preferred embodiment, a method for preparing a photodegradable impurity of Asartan Potassium comprises the following steps:

[0026] (1) The ground mesartan potassium raw material is evenly spread on a culture dish, placed in a UV light box, and destroyed in contact with air. The light intensity is 3000 to 6000 Lx, and the light duration is 40 to 60 h, thereby obtaining mesartan potassium light-destroyed product.

[0027] (2) adding acetone to the light-destructed product obtained in step (1), stirring, filtering, collecting the filtrate, and concentrating to obtain a photodegradable impurity-enriched product;

[0028] (3) using 200-300 mesh silica gel as filler and using dichloromethane and anhydrous methanol in a volume ratio of 20:1 as eluent, separating and purifying the photodegradation impurity enriched product obtained in step (2) by column chromatography, and collecting the elution effluent containing the target product;

[0029] (4) Concentrating the eluted effluent obtained in step (3), adding an organic solvent, heating to 40-50° C., stirring until dissolved and clarified, then cooling to 10-15° C., crystallizing, filtering, and drying to obtain the photodegradable impurity compound of potassium mesartan of formula I.

[0030] The present invention also provides the use of the photodegradation impurities of Asartan Potassium as impurity reference substances for Asartan Potassium APIs and preparations.

[0031] Another aspect of the present invention is to provide a method for detecting photodegradation impurities of Asartan Potassium, using high performance liquid chromatography, the detection method is as follows:

[0032] 1. Chromatographic conditions:

[0033] Chromatographic column: Octadecylsilane bonded silica gel as filler (XB-C18, 4.6mm×150mm, 3μm or chromatographic column with equivalent performance);

[0034] Mobile phase A: 0.05 mol / L potassium dihydrogen phosphate solution (take 6.8 g of potassium dihydrogen phosphate, add 1000 ml of water to dissolve, and adjust the pH value to 3.0 with phosphoric acid)-acetonitrile (95:5);

[0035] Mobile phase B: 0.05 mol / L potassium dihydrogen phosphate solution (take 6.8 g of potassium dihydrogen phosphate, add 1000 ml of water to dissolve, and adjust the pH value to 3.0 with phosphoric acid)-acetonitrile (30:70);

[0036] Detection wavelength: 240nm;

[0037] Flow rate: 1.0ml / min;

[0038] Injection volume: 10 μl;

[0039] Sample plate temperature: 5°C;

[0040] Column temperature: 25℃.

[0041] Gradient Program:

[0042] Time (minutes) Mobile phase A (%) Mobile phase B (%) 0 70 30 3 70 30 43 35 65 48 35 65 58 10 90 75 10 90 85 70 30

[0043] 2. Solution preparation:

[0044] Avoid light when operating.

[0045] Solvent: acetonitrile-water (80:20).

[0046] Test solution: Take about 2 mg of the product, weigh accurately, place in a 25 ml brown volumetric flask, add solvent to dissolve and dilute to the scale, and shake well.

[0047] The technical advantages of the present invention are:

[0048] (1) The present invention develops a method for preparing high-purity photodegradable impurities of sartan potassium, that is, the sartan potassium raw material is subjected to light destruction, enrichment, column chromatography separation, and recrystallization purification steps under air contact conditions to obtain photodegradable impurities with a purity of up to 99.6%;

[0049] (2) The photodegradation impurity of asesartan potassium described in the present invention is actually detected in the relevant substance inspection of the photostability test of asesartan potassium raw materials and preparations, and the detection values ​​are 0.23% and 0.25%, respectively. It is one of the main degradation impurities and is necessary to be studied. The present invention characterizes a new asesartan potassium impurity compound, confirms its structure, and develops a liquid phase detection method for the impurity. The impurity can be used as an impurity reference substance for asesartan potassium raw materials and preparations, and can be used for analysis, detection and quality control of asesartan potassium raw materials and preparations to ensure quality control and drug safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0051] Figure 1 This is the light destruction spectrum of Sino-US Asartan Potassium API in Example 1, in which the peak position of the photodegradation impurity is at the retention time of 30.977 min;

[0052] Figure 2 This is the light damage spectrum of Sino-American asartan potassium preparation in Example 2, wherein the peak position of the photodegradation impurity is at the retention time of 30.979 min;

[0053] Figure 3 is the HPLC spectrum of the compound of formula I in Example 3;

[0054] Figure 4 is the H NMR spectrum of the compound of formula I in Example 3;

[0055] Figure 5 is the NMR carbon spectrum of the compound of formula I in Example 3;

[0056] Figure 6 This is the LC-MS spectrum of the compound of formula I in Example 3. DETAILED DESCRIPTION

[0057] The present invention is further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only for illustrative purposes and are not intended to limit the present invention, which is obvious to those skilled in the art.

[0058] The raw material of Asartan Potassium used in the examples of the present invention is provided by Zhuhai Rundu Pharmaceutical Co., Ltd., with an HPLC purity of 98.6%; the preparation used in the examples is 80 mg Asartan Potassium tablets, purchased from the original manufacturer Takeda Pharmaceutical. Other reagents used, unless otherwise specified, are commonly used raw materials in this field and can be obtained through commercial channels. Unless otherwise specified, the test conditions are normal temperature, humidity and pressure environment in the laboratory.

[0059] The present invention provides HPLC detection method as follows:

[0060] 1. Chromatographic conditions:

[0061] Chromatographic column: Octadecylsilane bonded silica gel as filler (XB-C18, 4.6mm×150mm, 3μm or chromatographic column with equivalent performance);

[0062] Mobile phase A: 0.05 mol / L potassium dihydrogen phosphate solution (take 6.8 g of potassium dihydrogen phosphate, add 1000 ml of water to dissolve, and adjust the pH value to 3.0 with phosphoric acid)-acetonitrile (95:5);

[0063] Mobile phase B: 0.05 mol / L potassium dihydrogen phosphate solution (take 6.8 g of potassium dihydrogen phosphate, add 1000 ml of water to dissolve, and adjust the pH value to 3.0 with phosphoric acid)-acetonitrile (30:70);

[0064] Detection wavelength: 240nm;

[0065] Flow rate: 1.0ml / min;

[0066] Injection volume: 10 μl;

[0067] Sample plate temperature: 5°C;

[0068] Column temperature: 25℃.

[0069] Gradient Program:

[0070] Time (minutes) Mobile phase A (%) Mobile phase B (%) 0 70 30 3 70 30 43 35 65 48 35 65 58 10 90 75 10 90 85 70 30

[0071] 2. Solution preparation:

[0072] Avoid light when operating.

[0073] Solvent: acetonitrile-water (80:20).

[0074] Test solution: Take about 2 mg of the product, weigh accurately, place in a 25 ml brown volumetric flask, add solvent to dissolve and dilute to the scale, and shake well.

[0075] The method is used for the detection of compounds of formula I.

[0076] Example 1: Photodestruction test of Asartan potassium raw material

[0077] (1) Take about 11 mg of the raw material of mesartan potassium, place it in a 10 ml volumetric flask, add solvent to dissolve and dilute to the scale, shake well, and use it as the raw material undamaged test solution;

[0078] (2) Place the above 10 ml volumetric flask in a light box with an illumination of 4500 lx for 115 hours, dilute to the scale with solvent, and shake well to prepare the light-damaged test solution;

[0079] (3) Take a sample of the light-damaged test solution and record the chromatogram. Figure 1 As shown, the detected value of photodegradation impurity content of Asartan Potassium is 0.23%.

[0080] Example 2: Photodestruction test of Asartan potassium preparation

[0081] (1) Take 5 tablets of Asartan Potassium, place them in a 200 ml volumetric flask, add an appropriate amount of solvent, shake to dissolve Asartan Potassium, dilute to scale with solvent, shake well, and use this as the test sample stock solution;

[0082] (2) Take the stock solution of the test sample, filter it, and accurately measure 5 ml of the filtrate and place it in a 10 ml volumetric flask;

[0083] (3) Place the above 10 ml volumetric flask in a light box with an illumination of 4500 lx for 115 hours, dilute to the scale with solvent, and shake well to prepare the light-damaged test solution;

[0084] (4) Take a sample of the light-destroyed test solution and record the chromatogram. Figure 2 As shown, the detected value of photodegradation impurity content in Asartan Potassium Tablets is 0.25%.

[0085] Example 3: Preparation of impurity compound of formula I

[0086] (1) 15.0 g of ground mesartan potassium powder (D90 of about 10-20 μm) was evenly spread on a culture dish, and placed in a UV light box for destruction in contact with air, with a humidity of about 45%, a light intensity of 3000 Lx, and a light exposure time of 60 h to obtain mesartan potassium light-destroyed product;

[0087] (2) Add 150 ml of acetone to the photodegradable product, stir, filter, collect the filtrate, and concentrate to obtain 3.3 g of photodegradable impurity-enriched product;

[0088] (3) using 200-300 mesh silica gel as filler and using dichloromethane and anhydrous methanol in a volume ratio of 20:1 as eluent (total volume 8.3 L), column chromatography was used to separate and purify the above-mentioned photodegradation impurity enriched product, and the elution effluent containing the target product was collected;

[0089] (4) Concentrate the eluted solution obtained above, add 5 ml of methanol, heat to 40-50° C. and stir until dissolved and clarified, then cool to 10-15° C. to crystallize, filter and dry to obtain the photodegradation impurity compound of formula I mesartan potassium, with a mass of 50.5 mg. The HPLC spectrum, nuclear magnetic hydrogen spectrum, nuclear magnetic carbon spectrum and LC-MS spectrum of the obtained compound of formula I are as follows: Figure 3 to Figure 6 The sample was taken for HPLC detection, and the HPLC purity of the impurity compound of formula I was 99.6%.

[0090] 1 H NMR (400 MHz, DMSO-d6) δ H:7.685-7.698(d,1H),7.559-7.572(d,1H),7.475-7.487(d,1H),7.428-7.442(t,1H),7.354-7.379(t,1H),7.308-7.321( d, 1H), 7.199-7.221 (m, 3H), 6.892-6.906 (d, 2H), 5.625 (s, 2H), 4.572-4.606 (dd, 2H), 4.196 (s, 2H), 1.371-1.395 (t, 3H).

[0091] 13 C NMR (125 MHz, DMSO-d6) δ C : 173.551, 170.775, 169.776, 166.038, 158.791, 141.972, 140.683, 139.752, 136.556, 131.567, 130.827, 130.347, 129.454, 129.073, 127.265, 125.717, 123.833, 121.689, 121.048, 116.632, 66.913, 64.396, 46.966, 14.868.

[0092] MS: (+ESI) m / z: 515.2.

[0093] Example 4: Preparation of impurity compound of formula I

[0094] (1) 15.0 g of the ground mesartan potassium powder was evenly spread on a culture dish, and placed in a UV light box to destroy it in contact with air, with a humidity of about 45%, a light intensity of 5000 Lx, and a light exposure time of 50 h to obtain a mesartan potassium light-destroyed product;

[0095] (2) Add 150 ml of acetone to the photodegradable product, stir, filter, collect the filtrate, and concentrate to obtain 4.1 g of a photodegradable impurity-enriched product;

[0096] (3) using 200-300 mesh silica gel as filler and using dichloromethane and anhydrous methanol in a volume ratio of 10:1 as eluent (total volume 5.6 L), column chromatography was used to separate and purify the above-mentioned photodegradation impurity enriched product, and the elution effluent containing the target product was collected;

[0097] (4) Concentrate the eluted liquid obtained above, add 7 ml of dichloromethane, heat to 35-40°C, stir until dissolved and clarified, then cool to 10-15°C for crystallization, filter and dry to obtain the photodegradable impurity compound of formula I, 42.8 mg. Take a sample for HPLC detection, and the HPLC purity of the impurity compound of formula I is 99.2%.

[0098] Example 5: Preparation of impurity compound of formula I

[0099] (1) 15.0 g of the ground lasartan potassium raw material was evenly spread on a culture dish, and placed in a UV light box to be destroyed in contact with air, with a light intensity of 6000 Lx and a light duration of 40 h to obtain a lasartan potassium light-destroyed product;

[0100] (2) Add 180 ml of tetrahydrofuran to the photodestructible product, stir, filter, collect the filtrate, and concentrate to obtain 2.6 g of a photodegradable impurity-enriched product;

[0101] (3) using 200-300 mesh silica gel as filler and using dichloromethane and anhydrous methanol in a volume ratio of 8:1 as eluent (total volume 2.2 L), column chromatography was used to separate and purify the above-mentioned photodegradation impurity enriched product, and the elution effluent containing the target product was collected;

[0102] (4) Concentrate the eluted liquid obtained above, add 5 ml of methanol, heat to 50-60° C., stir until dissolved and clarified, then cool to 15-20° C. for crystallization, filter and dry to obtain the photodegradable impurity compound of formula I, 21.6 mg. Take a sample for HPLC detection, and the HPLC purity of the impurity compound of formula I is 99.5%.

[0103] Example 6: Preparation of impurity compound of formula I

[0104] (1) 10.0 g of the ground mesartan potassium powder was evenly spread on a culture dish, and placed in a UV light box to destroy it in contact with air. The light intensity was 5000 Lx, and the light duration was 16 h, to obtain a mesartan potassium light-destroyed product;

[0105] (2) Add 120 ml of tetrahydrofuran to the photodestructible product, stir, filter, collect the filtrate, and concentrate to obtain 1.6 g of a photodegradable impurity-enriched product;

[0106] (3) using 300-400 mesh silica gel as filler and using dichloromethane and anhydrous methanol in a volume ratio of 20:1 as eluent (total volume 9 L), column chromatography was used to separate and purify the above-mentioned photodegradation impurity enriched product, and the elution effluent containing the target product was collected;

[0107] (4) Concentrate the eluted solution obtained above, add 5 ml of ethanol, heat to 50-60° C. and stir until dissolved and clarified, then cool to 10-15° C. for crystallization, filter and dry to obtain the photodegradable impurity compound of formula I, 8.6 mg. Take a sample for HPLC detection, and the HPLC purity of the impurity compound of formula I is 92.0%.

[0108] Purity was improved by column chromatography.

[0109] In Example 6, the shorter the illumination time, the less mass of the degradation impurities produced, and the less mass, the more difficult it is to separate and purify by column chromatography.

[0110] Example 7: Preparation of impurity compound of formula I

[0111] (1) 10.0 g of the ground mesartan potassium powder was evenly spread on a culture dish, and placed in a UV light box to destroy it in contact with air. The light intensity was 3000 Lx, and the light duration was 50 h, to obtain a mesartan potassium light-destroyed product;

[0112] (2) Add 350 ml of dichloromethane to the photodestructible product, stir, filter, collect the filtrate, and concentrate to obtain 0.7 g of the photodegradable impurity-enriched product;

[0113] (3) using 200-300 mesh silica gel as filler and using dichloromethane and anhydrous methanol in a volume ratio of 15:1 as eluent (total volume 6.4 L), column chromatography was used to separate and purify the above-mentioned photodegradation impurity enriched product, and the elution effluent containing the target product was collected;

[0114] (4) Concentrate the eluted liquid obtained above, add dichloromethane (5 ml), heat to 35-40°C and stir until dissolved and clarified, then cool to 10-20°C for crystallization, filter and dry to obtain the photodegradable impurity compound of formula I, mass 12.2 mg. Take a sample for HPLC detection, the HPLC purity of the impurity compound of formula I is 98.6%.

[0115] Example 8: Preparation of impurity compound of formula I

[0116] (1) 10.0 g of the ground mesartan potassium raw material was evenly spread on a culture dish, and placed in a UV light box to be destroyed in contact with air, with a light intensity of 3000 Lx and a light duration of 45 h to obtain a mesartan potassium light-destroyed product;

[0117] (2) Add 250 ml of ethyl acetate to the photodegradable product, stir, filter, collect the filtrate, and concentrate to obtain 0.9 g of a photodegradable impurity-enriched product;

[0118] (3) using 200-300 mesh silica gel as filler and using dichloromethane and anhydrous methanol in a volume ratio of 12:1 as eluent (total volume 7.6 L), column chromatography was used to separate and purify the above-mentioned photodegradation impurity enriched product, and the elution effluent containing the target product was collected;

[0119] The eluted liquid obtained above was concentrated, 5 ml of acetone was added, the temperature was raised to 30-35°C and stirred until dissolved and clarified, then the temperature was lowered to 0-10°C for crystallization, filtered and dried to obtain the photodegradable impurity compound of formula I mesartan potassium, with a mass of 18.9 mg. Samples were taken for HPLC detection, and the HPLC purity of the impurity compound of formula I was 96.2%.

[0120] The impurity has poor solubility in dichloromethane and ethyl acetate solvents. When dichloromethane or ethyl acetate is used to enrich the impurity, the quality of the enriched product obtained is significantly smaller, which is not conducive to purification.

[0121] The inventors also investigated the effects of high temperature damage and oxidation damage tests and found that the degradation impurities did not appear under these two conditions.

[0122] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A photodegradable impurity of Asartan Potassium, characterized in that: Its structural formula is shown in Formula 1, 2. The method for preparing the photodegradable impurities of Asartan Potassium according to claim 1, characterized in that: The steps include: (1) subjecting the potassium permanganate powder to light destruction in contact with air; (2) adding an organic solvent to the light-destructed product obtained in step (1), stirring, filtering, collecting the filtrate, and concentrating to obtain a photodegradable impurity-enriched product; (3) separating and purifying the photodegradation impurity enriched product obtained in step (2) by column chromatography, and collecting the elution liquid containing the target product; (4) Concentrating the eluted effluent obtained in step (3), adding an organic solvent, heating and stirring until dissolved and clarified, then cooling and crystallizing, filtering and drying to obtain the photodegradable impurity compound of potassium asartan represented by formula I.

3. The preparation method according to claim 2, characterized in that: The potassium bissartan powder described in step (1) refers to the potassium bissartan powder obtained after grinding, the condition of contact with air refers to the contact of the potassium bissartan powder with air in the culture dish, and the light destruction refers to spreading the powder evenly on the culture dish and then placing it in an ultraviolet light box for illumination.

4. The preparation method according to claim 2, characterized in that: The illumination intensity of step (1) is 3000-6000Lx, and the illumination duration is 16-60h.

5. The preparation method according to claim 2, characterized in that: The organic solvent in step (2) is at least one of tetrahydrofuran, acetone, ethyl acetate and dichloromethane; The organic solvent in step (4) is at least one of dichloromethane, methanol, ethanol and acetone.

6. The preparation method according to claim 2, characterized in that: The column chromatography filler in step (3) is 200-300 mesh or 300-400 mesh silica gel.

7. The preparation method according to claim 2, characterized in that: The column chromatography eluent in step (3) is dichloromethane and anhydrous methanol in a volume ratio of 20:1 to 8:

1.

8. The preparation method according to claim 2, characterized in that: The heating temperature in step (4) is 30-60°C, and the cooling and crystallization temperature is 0-20°C.

9. Use of the photodegradation impurities of Asartan Potassium according to claim 1 as impurity reference substances for Asartan Potassium API and preparations.

10. A method for detecting photodegradation impurities of Asartan Potassium, characterized in that: Using high performance liquid chromatography: The chromatographic conditions are: Chromatographic column: octadecylsilane bonded silica gel as filler; Mobile phase A: 0.05 mol / L potassium dihydrogen phosphate solution-acetonitrile volume ratio 95:5, The preparation method of 0.05 mol / L potassium dihydrogen phosphate solution is as follows: take 6.8 g of potassium dihydrogen phosphate, add 1000 ml of water to dissolve, and adjust the pH value to 3.0 with phosphoric acid; Mobile phase B: 0.05 mol / L potassium dihydrogen phosphate solution-acetonitrile volume ratio of 30:70; Detection wavelength: 240nm; Flow rate: 1.0ml / min; Sample plate temperature: 5°C; Gradient Program: Solution preparation: Keep away from light; Solvent: acetonitrile-water 80:20; Test solution: Take 2 mg of the product, weigh accurately, place in a 25 ml brown volumetric flask, add solvent to dissolve and dilute to the scale, shake well.

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