Method for detecting ornithine aspartate isomer

Abstract

The invention discloses a method for detecting ornithine aspartate isomers. The method comprises the following steps: carrying out high performance liquid chromatography detection on a sample to be detected; based on a detection result, determining whether the to-be-detected sample contains the ornithine isomer or not and the content of the ornithine isomer; wherein a mobile phase of the high performance liquid chromatography detection comprises copper acetate and ammonium acetate; the pH (Potential of Hydrogen) value of the mobile phase is 6.0 to 8.0. The method is high in detection result sensitivity, high in accuracy, low in detection limit, high in separation degree, safe, effective, good in stability, easy, convenient and rapid to operate and suitable for large-scale application.

Description

Technical Field

[0001] The present application relates to the field of medicine, and in particular to a method for detecting ornithine aspartate isomers and a quality control method for ornithine aspartate drugs. Background Art

[0002] Ornithine aspartate is an amino acid drug, mainly used to improve liver function and reduce blood ammonia. The chemical structure of ornithine aspartate is as follows:

[0003]

[0004] Ornithine aspartate injection can be used to treat or prevent elevated blood ammonia caused by acute or chronic liver diseases (such as various types of hepatitis, cirrhosis, fatty liver, and post-hepatitis syndrome) and to treat hepatic encephalopathy, such as latent or acute hepatic encephalopathy associated with or secondary to impaired liver detoxification function (such as cirrhosis). It is especially suitable for treating the early stages of hepatic coma or the state of confusion in hepatic coma.

[0005] More than 40% of the drugs in the world are chiral. Since human organs and cells are selective for the optical isomers of drugs, isomers may have various manifestations in the body: (1) One is effective and the other is ineffective: for example, salbutamol and terbutaline are two bronchodilators. The R-configuration of salbutamol is 80 times more potent than the S-configuration, and the R-configuration of terbutaline is 200 times more potent than the S-configuration; (2) One is effective and the other is ineffective, antagonistic, or toxic: the dextrorotatory isomer of thalidomide has therapeutic effects and can reduce early pregnancy reactions in pregnant women, but its levorotatory isomer is teratogenic; (3) The two configurations have completely different effects: for example, dextrorotatory propoxyphene is a sedative, while its levorotatory isomer is a cough suppressant; timolol is a β-receptor blocker. Its S configuration is used to treat hypertension and angina pectoris, while its R configuration is used to treat glaucoma.

[0006] Since ornithine aspartate has two chiral centers, L-aspartic acid and L-ornithine are used clinically. It is necessary to detect and control the isomers D-aspartic acid and D-ornithine in ornithine aspartate drugs to ensure drug safety and product quality. Therefore, it is necessary to develop an analytical method for isomers in ornithine aspartate. Summary of the invention

[0007] The present application aims to solve at least one of the technical problems existing in the prior art to a certain extent. To this end, the present application provides a method for detecting ornithine aspartate isomers, which can effectively detect isomers in ornithine aspartate, has the advantages of high sensitivity, high accuracy, low detection limit, high separation, safety, effectiveness, good stability, simple and fast operation, etc., and is suitable for wide application.

[0008] This application is completed based on the following findings of the inventors:

[0009] At present, the pharmacopoeias of various countries do not include analytical methods for the determination of D-aspartic acid and D-ornithine in ornithine aspartate raw materials and preparations. Patent CN117434176A discloses a separation and determination method for isomers in ornithine aspartate and the document "Quality Research of Ornithine Aspartate Injection" involves analytical methods for the determination of D-aspartic acid and D-ornithine in ornithine aspartate raw materials and preparations, but the pH value of the mobile phase in the above method is 1.0, and the instrument's lowest tolerance pH is about 2.0. Since the pH value of the mobile phase is too low, it will corrode the instrument. At the same time, this method uses perchloric acid as the mobile phase, which is an explosive chemical, and there are certain safety risks in the operation process. In addition, although the document "HPLC Method for Determination of the Content of Two Isomers in Ornithine Aspartate Raw Materials" discloses an analytical method for the determination of D-aspartic acid and D-ornithine in ornithine aspartate raw materials and preparations, in this method, ornithine aspartate (L-aspartic acid and L-ornithine) peaks first and isomers (D-aspartic acid and D-ornithine) peak later, and the peaks are severely tailed, affecting the separation degree. Secondly, the reproducibility of this method is not high.

[0010] Based on this, in one aspect of the present application, the present application proposes a method for detecting ornithine aspartate isomers. According to an embodiment of the present application, the method comprises:

[0011] The sample to be tested is subjected to high performance liquid chromatography detection;

[0012] Based on the test results, determining whether guanidine isomers and the content of guanidine isomers are present in the sample to be tested;

[0013] Wherein, the mobile phase for the high performance liquid chromatography detection comprises copper acetate and ammonium acetate;

[0014] The pH value of the mobile phase is 6.0-8.0.

[0015] When using high performance liquid chromatography to detect ornithine aspartate, the inventor unexpectedly discovered that the composition of the mobile phase will significantly affect the separation effect of ornithine aspartate isomers. If the mobile phase is not selected properly, ornithine aspartate and the isomers cannot be separated, thereby failing to achieve the purpose of accurate separation and detection, and further making it more difficult to determine the specific content. In the method of the present application, copper acetate and ammonium acetate are used as mobile phases, and the pH value of the mobile phase is 6.0 to 8.0, which can effectively separate and detect isomers in ornithine aspartate. The content of isomers in ornithine aspartate can also be calculated based on the obtained liquid chromatogram. Therefore, the detection results of the method of the present application are highly sensitive, highly accurate, have a low detection limit, have a high degree of separation, are safe, effective, have good stability, are easy to operate, and are quick, and are suitable for large-scale applications.

[0016] As used herein, "ornithine aspartate" or "ornithine aspartate drug" refers to L-aspartic acid and L-ornithine; "ornithine aspartate isomer" refers to D-aspartic acid and D-ornithine.

[0017] According to an embodiment of the present application, the above method further includes at least one of the following technical features:

[0018] According to an embodiment of the present application, the concentration of copper acetate in the mobile phase is 0.03-0.08 mM, for example, 0.03 mM, 0.04 mM, 0.05 mM, 0.06 mM, 0.07 mM, 0.08 mM and any two of them as the range value between the endpoint values.

[0019] According to an embodiment of the present application, the concentration of copper acetate in the mobile phase is 0.04-0.06 mM.

[0020] According to an embodiment of the present application, the concentration of ammonium acetate in the mobile phase is 0.05-0.15 mM, for example, 0.05 mM, 0.06 mM, 0.07 mM, 0.08 mM, 0.09 mM, 0.10 mM, 0.11 mM, 0.12 mM, 0.13 mM, 0.14 mM, 0.15 mM and any two point values ​​thereof as the range value between the endpoint values.

[0021] According to an embodiment of the present application, the concentration of ammonium acetate in the mobile phase is 0.09-0.11 mM.

[0022] According to an embodiment of the present application, the elution method in the HPLC detection is isocratic elution.

[0023] According to an embodiment of the present application, the detection wavelength used in the high performance liquid chromatography detection is 230nm~270nm, for example, 230nm, 235nm, 240nm, 245nm, 250nm, 255nm, 260nm, 265nm, 270nm and any two point values ​​therein as the range value between the endpoint values.

[0024] According to an embodiment of the present application, the column temperature used in the high performance liquid chromatography detection is 10°C to 30°C, for example, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C and any two of them as the range value between the endpoint values.

[0025] According to an embodiment of the present application, the chromatographic column used in the high performance liquid chromatography detection is SCASSUMICHIRAL OA-5000L.

[0026] According to an embodiment of the present application, the flow rate used in the HPLC detection is 0.70 mL / min to 0.90 mL / min.

[0027] According to an embodiment of the present application, the sample to be tested is selected from ornithine aspartate injection.

[0028] In another aspect of the present application, the present application proposes a quality control method for ornithine aspartate drugs. According to an embodiment of the present application, the method includes: using the aforementioned method to detect ornithine aspartate isomers in the ornithine aspartate drug to be tested; based on the test results, determining whether the quality of the ornithine aspartate drug to be tested is qualified. Therefore, the method of the present application can accurately determine whether the ornithine aspartate isomer sample meets the requirements, thereby effectively ensuring drug safety and controlling product quality.

[0029] According to an embodiment of the present application, the ornithine aspartate drug to be tested is ornithine aspartate injection.

[0030] According to an embodiment of the present application, before the detection, the ornithine aspartate drug to be tested is diluted in advance.

[0031] In an optional embodiment of the present application, the dilution factor of the dilution treatment is 5 to 20 times, for example, 5 times, 6 times, 7 times, 8 times, 9 times, 10 times, 11 times, 12 times, 13 times, 14 times, 15 times, 16 times, 17 times, 18 times, 19 times, and 20 times.

[0032] In an optional embodiment of the present application, when the content of ornithine aspartate isomers in the ornithine aspartate injection sample is not greater than 0.5%, the ornithine aspartate injection sample is of qualified quality;

[0033] When the content of ornithine aspartate isomers in the ornithine aspartate injection sample is greater than 0.5%, the quality of the ornithine aspartate injection sample is unqualified.

[0034] In another aspect of the present application, the present application proposes a quality control method for ornithine aspartate drugs. According to an embodiment of the present application, the method comprises:

[0035] diluting the ornithine aspartate injection sample to obtain a test solution;

[0036] The liquid to be tested is subjected to high performance liquid chromatography to determine the content of ornithine aspartate isomers in the liquid to be tested;

[0037] When the content of ornithine aspartate isomers in the ornithine aspartate injection sample is not greater than 0.5%, the ornithine aspartate injection sample is of qualified quality;

[0038] When the content of ornithine aspartate isomers in the ornithine aspartate injection sample is greater than 0.5%, the quality of the ornithine aspartate injection sample is unqualified;

[0039] Wherein, the mobile phase for the high performance liquid chromatography detection comprises copper acetate and ammonium acetate;

[0040] The pH value of the mobile phase is 6.0 to 8.0;

[0041] The concentration of copper acetate in the mobile phase is 0.04-0.06 mM;

[0042] The concentration of ammonium acetate in the mobile phase is 0.09-0.11 mM;

[0043] The elution method in the high performance liquid chromatography detection is isocratic elution;

[0044] The detection wavelength used in the high performance liquid chromatography detection is 230nm to 270nm;

[0045] The column temperature used in the high performance liquid chromatography detection is 10°C to 30°C;

[0046] The chromatographic column used in the high performance liquid chromatography detection is SCAS SUMICHIRAL OA-5000L;

[0047] The flow rate used in the high performance liquid chromatography detection is 0.70 mL / min to 0.90 mL / min.

[0048] Therefore, the method of the present application can accurately determine whether the ornithine aspartate isomer sample meets the requirements, thereby effectively ensuring drug safety and controlling product quality.

[0049] Additional aspects and advantages of the present application will be given in part in the description below, and in part will become apparent from the description below, or will be learned through the practice of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] The above and / or additional aspects and advantages of the present application will become apparent and easily understood from the description of the embodiments in conjunction with the following drawings, in which:

[0051] Figure 1 This is the HPLC chromatogram in Example 1 of the present application;

[0052] Figure 2 This is the HPLC chromatogram with a column temperature of 22° C. in Example 2 of the present application;

[0053] Figure 3 This is the HPLC chromatogram with a column temperature of 18° C. in Example 2 of the present application;

[0054] Figure 4 This is the HPLC chromatogram of the mobile phase of 0.03 mM copper acetate + 0.1 M ammonium acetate in Example 2 of the present application;

[0055] Figure 5 This is the HPLC chromatogram of the mobile phase of 0.08 mM copper acetate + 0.1 M ammonium acetate in Example 2 of the present application;

[0056] Figure 6 This is the HPLC chromatogram of the mobile phase of 0.05 mM copper acetate + 0.07 M ammonium acetate in Example 2 of the present application;

[0057] Figure 7 This is the HPLC chromatogram of the mobile phase of 0.05 mM copper acetate + 0.13 M ammonium acetate in Example 2 of the present application;

[0058] Figure 8 This is the HPLC chromatogram at a flow rate of 0.85 ml / min in Example 2 of the present application;

[0059] Fig. 9 This is the HPLC chromatogram at a flow rate of 0.75 ml / min in Example 2 of the present application;

[0060] Fig.10 This is the HPLC chromatogram with a detection wavelength of 255 nm in Example 2 of the present application;

[0061] Fig.11This is the HPLC chromatogram with a detection wavelength of 253 nm in Example 2 of the present application. DETAILED DESCRIPTION

[0062] The embodiments of the present application are described in detail below. The embodiments described below are exemplary and are only used to explain the present application, and cannot be understood as limiting the present application.

[0063] It should be noted that the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. Further, in the description of this application, unless otherwise specified, the meaning of "plurality" is two or more.

[0064] In this document, the terms "include" or "comprising" are open expressions, that is, including the contents specified in the present application but not excluding other contents.

[0065] As used herein, the terms "optionally", "optional" or "optionally" generally mean that the subsequently described event or circumstance may but need not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not.

[0066] The scheme of the present application will be explained below in conjunction with the embodiments. It will be appreciated by those skilled in the art that the following embodiments are only used to illustrate the present application and should not be considered as limiting the scope of the present application. If no specific technology or conditions are indicated in the embodiments, the technology or conditions described in the literature in this area or the product specification are carried out. The reagents used or the instruments that do not indicate the manufacturer are all conventional products that can be obtained commercially.

[0067] Example 1: Detection of ornithine aspartate isomers

[0068] The experimental steps are as follows:

[0069] Preparation of mobile phase: accurately weigh 0.091g of copper acetate and 7.7g of ammonium acetate, dissolve them in water, and dilute to 1000ml with water;

[0070] Preparation of sample solution: Accurately measure 2 ml of the test sample (commercially available ornithine aspartate injection, the same below), place it in a 250 ml volumetric flask, dilute to the scale with water, shake well, and obtain.

[0071] Detection: Take 5 μl of sample solution and inject it into liquid chromatograph. Use Agilent 1260Ⅱ high performance liquid chromatograph for detection. The chromatographic conditions are as follows:

[0072] Chromatographic column: SCAS SUMICHIRAL OA-5000L, 4.6×250 mm, 5 μm;

[0073] Column temperature: 20°C;

[0074] Mobile phase: 0.05 mM copper acetate + 0.1 M ammonium acetate aqueous solution;

[0075] Flow rate: 0.8ml / min;

[0076] Injection volume: 5 μl;

[0077] Detection wavelength: 254nm.

[0078] Record the chromatogram, see Figure 1 .

[0079] The chromatographic results show that aspartate ornithine isomers (D-aspartate, D-ornithine) elute first, and aspartate ornithine (L-aspartate and L-ornithine) elute later. The separation degree between D-ornithine and L-ornithine is 2.1, and the separation degree between D-aspartate and L-aspartate is 1.8. The good separation degree can avoid the tailing of the aspartate ornithine main peak affecting the detection of the isomer peaks.

[0080] Example 2: Screening by detection method

[0081] 1. Adjustment of column temperature

[0082] Preparation of mobile phase: accurately weigh 0.091g of copper acetate and 7.7g of ammonium acetate, dissolve them in water, and dilute to 1000ml with water;

[0083] Preparation of sample solution: Accurately measure 2 ml of the test sample (ornithine aspartate injection), place it in a 250 ml volumetric flask, dilute to the scale with water, shake well, and obtain.

[0084] Detection: Take 5 μl of sample solution and inject it into liquid chromatograph. Use Agilent 1260Ⅱ high performance liquid chromatograph for detection. The chromatographic conditions are as follows:

[0085] Chromatographic column: SCAS SUMICHIRAL OA-5000L, 4.6×250 mm, 5 μm;

[0086] Column temperature: 22℃ and 18℃ ;

[0087] Mobile phase: 0.05 mM copper acetate + 0.1 M ammonium acetate aqueous solution;

[0088] Flow rate: 0.8ml / min;

[0089] Injection volume: 5 μl;

[0090] Detection wavelength: 254nm.

[0091] Record the chromatograms. The column temperatures are 22°C and 18°C. Figure 2 , Figure 3 .

[0092] From the spectrum, we can see that the separation degree of D-aspartic acid and L-aspartic acid is 1.7 when the column temperature is 22℃ and 18℃, and when the column temperature is 20℃.

[0093] (2) Adjustment of mobile phase ratio

[0094] Preparation of mobile phase: see Example 1;

[0095] Preparation of sample solution: Accurately measure 2 ml of the test sample (ornithine aspartate injection), place it in a 250 ml volumetric flask, dilute to the scale with water, shake well, and obtain.

[0096] Detection: Take 5 μl of sample solution and inject it into liquid chromatograph. Use Agilent 1260Ⅱ high performance liquid chromatograph for detection. The chromatographic conditions are as follows:

[0097] Chromatographic column: SCAS SUMICHIRAL OA-5000L, 4.6×250 mm, 5 μm;

[0098] Column temperature: 20°C;

[0099] Mobile Phase: 0.03mM copper acetate + 0.1M ammonium acetate aqueous solution, 0.08mM copper acetate + 0.1M ammonium acetate aqueous solution, 0.05mM copper acetate + 0.07M ammonium acetate aqueous solution, 0.05mM copper acetate + 0.13M ammonium acetate aqueous solution ;

[0100] Flow rate: 0.8ml / min;

[0101] Injection volume: 5 μl;

[0102] Detection wavelength: 254nm.

[0103] Record the chromatogram, such as Figure 4 (0.03mM copper acetate + 0.1M ammonium acetate aqueous solution), Figure 5 (0.08mM copper acetate + 0.1M ammonium acetate aqueous solution), Figure 6 (0.05mM copper acetate + 0.07M ammonium acetate aqueous solution), Figure 7 (0.05 mM copper acetate + 0.13 M ammonium acetate aqueous solution).

[0104] From the spectrum, we can see that under the conditions of 0.03mM copper acetate + 0.1M ammonium acetate aqueous solution, 0.08mM copper acetate + 0.1M ammonium acetate aqueous solution, 0.05mM copper acetate + 0.07M ammonium acetate aqueous solution, and 0.05mM copper acetate + 0.13M ammonium acetate aqueous solution, the separation degree is 1.7 when 0.03mM copper acetate + 0.1M ammonium acetate aqueous solution, and the separation degree is 1.4; when 0.08mM copper acetate + 0.1M ammonium acetate aqueous solution, the separation degree is 1.4, and the separation degree is 1.4; when 0.05mM copper acetate + 0.07M ammonium acetate aqueous solution, the separation degree is 2.0, and the separation degree is 1.4; when 0.05mM copper acetate + 0.13M ammonium acetate aqueous solution, the separation degree is 1.7, and the separation degree is 1.7.

[0105] (3) Flow rate screening

[0106] Preparation of mobile phase: accurately weigh 0.091g of copper acetate and 7.7g of ammonium acetate, dissolve them in water, and dilute to 1000ml with water;

[0107] Preparation of sample solution: Accurately measure 2 ml of the test sample (ornithine aspartate injection), place it in a 250 ml volumetric flask, dilute to the scale with water, shake well, and obtain.

[0108] Detection: Take 5 μl of sample solution and inject it into liquid chromatograph. Use Agilent 1260Ⅱ high performance liquid chromatograph for detection. The chromatographic conditions are as follows:

[0109] Chromatographic column: SCAS SUMICHIRAL OA-5000L, 4.6×250 mm, 5 μm;

[0110] Column temperature: 20°C;

[0111] Mobile phase: 0.05 mM copper acetate + 0.1 M ammonium acetate aqueous solution;

[0112] Flow Rate: 0.85ml / min、0.75ml / min ;

[0113] Injection volume: 5 μl;

[0114] Detection wavelength: 254nm.

[0115] Record the chromatograms. The flow rates are 0.85 ml / min and 0.75 ml / min. Figure 8 , Fig. 9 .

[0116] From the spectrum, we can see that at a flow rate of 0.85 ml / min, the separation degree of D-ornithine and L-ornithine is 2.0, and the separation degree of D-aspartic acid and L-aspartic acid is 1.8; when the flow rate is 0.75 ml / min, the separation degree of D-ornithine and L-ornithine is 2.0, and the separation degree of D-aspartic acid and L-aspartic acid is 1.8.

[0117] (4) Wavelength selection

[0118] Preparation of mobile phase: accurately weigh 0.091g of copper acetate and 7.7g of ammonium acetate, dissolve them in water, and dilute to 1000ml with water;

[0119] Preparation of sample solution: Accurately measure 2 ml of the test sample (ornithine aspartate injection), place it in a 250 ml volumetric flask, dilute to the scale with water, shake well, and obtain.

[0120] Detection: Take 5 μl of sample solution and inject it into liquid chromatograph. Use Agilent 1260Ⅱ high performance liquid chromatograph for detection. The chromatographic conditions are as follows:

[0121] Chromatographic column: SCAS SUMICHIRAL OA-5000L, 4.6×250 mm, 5 μm;

[0122] Column temperature: 20°C;

[0123] Mobile phase: 0.05 mM copper acetate + 0.1 M ammonium acetate aqueous solution;

[0124] Flow rate: 0.8ml / min;

[0125] Injection volume: 5 μl;

[0126] Detection wavelength: 255nm、253nm .

[0127] Record the chromatogram, and the detection wavelengths are 255nm and 253nm respectively. Fig.10 , Fig.11 .

[0128] From the spectrum, it can be seen that there is no significant difference in the separation between impurities and the main peak at wavelengths of 255nm, 253nm and 254nm, and there is no significant difference in the detection amount of impurities, indicating that the wavelength durability of this method is good.

[0129] Example 3: Methodological Investigation

[0130] The detection method of Example 1 was methodologically verified by conventional methods in the art from the aspects of system adaptability, specificity, detection limit, quantification limit, linear range, accuracy, repeatability, precision, stability and durability. The specific test results are as follows:

[0131]

[0132]

[0133] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present application. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0134] Although the embodiments of the present application have been shown and described above, it can be understood that the above embodiments are exemplary and cannot be understood as limitations on the present application. Ordinary technicians in this field can change, modify, replace and modify the above embodiments within the scope of the present application.

Claims

1. A method for detecting ornithine aspartate isomers, characterized in that: include: The sample to be tested is subjected to high performance liquid chromatography detection; Based on the test results, determining whether guanidine isomers and the content of guanidine isomers are present in the sample to be tested; Wherein, the mobile phase for the high performance liquid chromatography detection comprises copper acetate and ammonium acetate; The pH value of the mobile phase is 6.0-8.

0.

2. The method according to claim 1, characterized in that The concentration of copper acetate in the mobile phase is 0.03-0.08 mM; and / or, the concentration of ammonium acetate in the mobile phase is 0.05 to 0.15 mM; And / or, the elution method in the high performance liquid chromatography detection is isocratic elution; And / or, the detection wavelength used in the high performance liquid chromatography detection is 230nm to 270nm; And / or, the column temperature used in the high performance liquid chromatography detection is 10°C to 30°C; And / or, the chromatographic column used in the high performance liquid chromatography detection is SCAS SUMICHIRAL OA-5000L; And / or, the flow rate used in the high performance liquid chromatography detection is 0.70 mL / min to 0.90 mL / min.

3. The method according to claim 1, characterized in that The concentration of copper acetate in the mobile phase is 0.04-0.06 mM.

4. The method according to claim 1, characterized in that: The concentration of ammonium acetate in the mobile phase is 0.09-0.11 mM.

5. The method according to claim 1, characterized in that The sample to be tested is selected from ornithine aspartate injection.

6. A method for quality control of ornithine aspartate medicine, characterized in that: include: The method according to any one of claims 1 to 5 is used to detect the isomers of ornithine aspartate in the ornithine aspartate drug to be tested; Based on the test results, determine whether the quality of the ornithine aspartate drug to be tested is qualified.

7. The method according to claim 6, characterized in that The content of ornithine aspartate isomers in the ornithine aspartate drug to be tested being no greater than 0.5% is an indication that the ornithine aspartate drug to be tested is of qualified quality.

8. The method according to claim 6, characterized in that The ornithine aspartate drug to be tested is ornithine aspartate injection.

9. The method according to claim 6, characterized in that Before the detection, the ornithine aspartate drug to be detected is diluted in advance.

10. A method for quality control of ornithine aspartate medicine, characterized in that: include: diluting the ornithine aspartate injection sample to obtain a test solution; The liquid to be tested is subjected to high performance liquid chromatography to determine the content of ornithine aspartate isomers in the liquid to be tested; When the content of ornithine aspartate isomers in the ornithine aspartate injection sample is not greater than 0.5%, the ornithine aspartate injection sample is of qualified quality; When the content of ornithine aspartate isomers in the ornithine aspartate injection sample is greater than 0.5%, the quality of the ornithine aspartate injection sample is unqualified; Wherein, the mobile phase for the high performance liquid chromatography detection comprises copper acetate and ammonium acetate; The pH value of the mobile phase is 6.0 to 8.0; The concentration of copper acetate in the mobile phase is 0.04-0.06 mM; The concentration of ammonium acetate in the mobile phase is 0.09-0.11 mM; The elution method in the high performance liquid chromatography detection is isocratic elution; The detection wavelength used in the high performance liquid chromatography detection is 230nm to 270nm; The column temperature used in the high performance liquid chromatography detection is 10°C to 30°C; The chromatographic column used in the high performance liquid chromatography detection is SCAS SUMICHIRAL OA-5000L; The flow rate used in the high performance liquid chromatography detection is 0.70 mL / min to 0.90 mL / min.

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