A kind of analytical method for detecting aspartic acid ornithine impurity

A technology of ornithine aspartate and analytical method, applied in the field of analytical chemistry, can solve the problem that the quantitative and qualitative methods are not clearly included, and the dimerized arginine and α-aspartic acid dimer gates are not disclosed. Qualitative and quantitative analysis methods of aspartic acid condensate to achieve good separation

Active Publication Date: 2020-10-27
SHANDONG INST FOR FOOD & DRUG CONTROL
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Problems solved by technology

[0004] Regarding the detection method of impurities in aspartic acid ornithine, CN104807924A aspartic acid ornithine raw material and preparation specific impurity detection method provides a method for accurately analyzing and detecting the aspartic acid ornithine prepared by the synthesis process. Contained impurities: a high-efficiency liquid phase analysis and detection method for fumaric acid, arginine, urea, succinic acid, malic acid, and lactam; CN102288687A An analysis and detection method for aspartic acid ornithine impurities also only provides Ornithine or impurity ornithine-containing drugs and preparations of ornithine detection method; the above patents do not disclose dimer arginine, α-aspartic acid dimer, aspartic acid condensation Qualitative and quantitative analysis methods of substances
Moreover, the quantitative and qualitative methods for the above four impurities are not clearly included in the existing drug quality standards for aspartic acid ornithine and its preparations. This application is mainly aimed at the qualitative and quantitative methods of the above four impurities. Research

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  • A kind of analytical method for detecting aspartic acid ornithine impurity
  • A kind of analytical method for detecting aspartic acid ornithine impurity
  • A kind of analytical method for detecting aspartic acid ornithine impurity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1 Detection of resolution

[0049] 1). Specific experimental operations:

[0050] Positioning solution of each impurity reference substance: accurately weigh out 10mg each of 3-amino-2-piperidone, α-aspartic acid dimer, aspartic acid condensate, and dimer arginine, and put them into 50ml measuring bottles. In the medium, add mobile phase B to dissolve and dilute to the mark, shake well, and get ready.

[0051] Positioning solution of the test product: accurately weigh 100 mg of ornithine hydrochloride, aspartic acid, and ornithine aspartate, respectively, put them in a 10ml measuring flask, add mobile phase B to dissolve and dilute to the mark, shake well, that is Got.

[0052] Mixed solution: accurately weigh ornithine aspartate, place it in a 10ml measuring flask, accurately measure 3-amino-2-piperidone, α-aspartic acid dimer, aspartic acid condensate, Place each 0.5ml of the dimer arginine reference substance positioning solution in the same place, add mobile phase...

Embodiment 2

[0058] Example 2 Measurement of linear range

[0059] 1) Solution configuration

[0060] Precisely weigh 10mg each of α-aspartic acid dimer, aspartic acid condensate, and dimer arginine, put them in a 10ml volumetric flask, add an appropriate amount of solvent to dissolve and dilute to the mark, shake well, as impurities Linear stock solution.

[0061] Precisely weigh each 10mg of aspartic acid and ornithine, and place them in a 10ml measuring flask. Precisely add 2ml of the above-mentioned impurity linear stock solution and place in a 100ml measuring flask. Add an appropriate amount of solvent to dissolve and dilute to the mark. Shake well, as linear Test solution 1#.

[0062] Precisely measure linear test solution 1#8ml, 7ml, 6ml, 5ml, 4ml, 3ml, 2.5ml, 1ml, 0.5ml, put them into 10ml measuring flasks, add solvent to dilute to the mark, shake well, and use as linear test solution 2# , 3#, 4#, 5#, 6#, 7#, 8#, 9#, 10#.

[0063] Precisely weigh 40 mg of 3-amino-2-piperidone and place it...

Embodiment 3

[0088] Example 3 Determination of detection limit

[0089] 1), the method of detection limit determination

[0090] Configuration of detection limit solution: Dilute the linear stock solution of each impurity in Example 2 step by step, and obtain the solution when S / N≈3 as the detection limit solution;

[0091] 2), measurement results

[0092] Precisely take 20μl of the blank solution and inject it into the liquid chromatograph; Precisely take 20μl of the above-mentioned limit of quantification solution, inject it into the liquid chromatograph, and inject 3 times continuously, record the chromatogram, take S / N≈3 as the detection limit, and the statistics are as follows .

[0093] Table 8: Detection limit test results

[0094]

[0095] Test results: The detection limit of aspartic acid condensate was 0.6ng, the detection limit of α-aspartic acid dimer was 1.0ng, the detection limit of dimer arginine was 3.4ng, and the detection limit of ornithine was 16.7ng. The detection limit of aspar...

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Abstract

The invention discloses an analysis method for detecting impurities in aspartic acid ornithine, which belongs to the field of analytical chemistry; the method adopts liquid chromatography, amino-bonded silica gel filler, Thermo APS‑2 4.6×250mm, 5 μm, and 0.1mol / L potassium dihydrogen phosphate buffer-acetonitrile (35:65) is mobile phase A, 0.1mol / L potassium dihydrogen phosphate buffer-acetonitrile (50:50) is mobile phase B; the detection wavelength is 200nm; The flow rate is 1.0ml per minute; the column temperature is 30°C, and gradient elution is used for analysis. This technical solution can quickly and accurately detect 3‑amino‑2‑piperidone and dimer arginine in impurities aspartic acid ornithine acid, α-aspartic acid dimer, and aspartic acid condensate for qualitative and quantitative analysis, and the resolution is good, the detection limit and quantification limit are low, and the linear range is wide, so that it can be calculated more accurately The content of different impurities provides technical support for further monitoring and research of impurities in ornithine-aspartate.

Description

[0001] Technical Field: The present invention belongs to the field of analytical chemistry, and specifically relates to a method for the analysis and detection of ornithine aspartate impurities using HPLC method, and more specifically, to a method for the analysis and detection of ornithine aspartate in 3- Amino-2-piperidone, dimer arginine, α-aspartic acid dimer, aspartic acid condensate four impurities method. Background technique: [0002] Ornithine aspartate (chemical name is (S)-2,5-diaminovaleric acid (s)-2-aminosuccinate), used clinically in Germany in the 1970s, and collected in 1991 The German Pharmacopoeia was imported and marketed in China in 2000. It was produced and marketed by domestic manufacturers in 2006. It is used to treat hyperammonemia caused by liver disease. Ornithine aspartate can provide a substrate for the synthesis of urea and glutamine in the body. Under physiological and pathological conditions, the synthesis of urea and the synthesis of glutamine wil...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): G01N30/02G01N30/06
CPCG01N30/02G01N30/06
Inventor 张冬梅牛冲于明艳赵海云李玉杰冷佳蔚
Owner SHANDONG INST FOR FOOD & DRUG CONTROL
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