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CN-121994961-A - Domperidone impurity detection method

CN121994961ACN 121994961 ACN121994961 ACN 121994961ACN-121994961-A

Abstract

The invention belongs to the field of pharmaceutical preparations, and particularly relates to a domperidone impurity detection method. The domperidone impurity detection method provided by the invention can detect the impurity A, the impurity B, the impurity C, the impurity D+E, the impurity F, the impurity H, the impurity I and the impurity J in domperidone, has high peak separation degree of each impurity, and can simultaneously detect the content of each impurity. The detection method provided by the invention has the advantages of good specificity, high sensitivity, good linearity, repeatability, solution stability, accuracy investigation and other experimental verification results. The result provides a new method for detecting the impurities of domperidone and provides a guarantee for the preparation of domperidone tablets and other preparations.

Inventors

  • YAN JING
  • CHANG ZHIHUA
  • Cai Chunnuan
  • Liao Kelin

Assignees

  • 海南亚洲制药股份有限公司

Dates

Publication Date
20260508
Application Date
20260222

Claims (10)

  1. 1. The domperidone impurity detection method is characterized by comprising the following steps: (1) Preparation of test solutions Taking domperidone to be detected, dissolving the domperidone with N, N-dimethylformamide and diluting the domperidone to be detected to prepare a solution to be detected; (2) Assay Precisely measuring the solution to be tested, injecting the solution into a high performance liquid chromatograph, taking 0.5% ammonium acetate solution as a mobile phase A and methanol as a mobile phase B, performing gradient elution at a flow rate of 1.0-1.5ml/min and a column temperature of 30-50 ℃ to separate domperidone from impurities, detecting the separated impurities and obtaining a chromatogram, wherein the gradient elution procedure is as follows: time (min) Mobile phase a (%) Mobile phase B (%) 0 70 30 0-10 70 Is decremented to 0 30 Is decreased to 100 10-12 Hold 0 Hold 100 12-12.01 0 Is increased to 70 100 Is decreased to 30 12.01-17 Holder 70 Holding 30 。
  2. 2. The method for detecting impurities in domperidone according to claim 1, wherein in the step (1), domperidone to be detected is dissolved and diluted with N, N-dimethylformamide to prepare a solution containing 10mg of domperidone per 1ml, in the step (2), the chromatographic column is Hypersil BDS C18, the inner diameter of the chromatographic column is 4.6mm, the length is 100mm, octadecylsilane bonded silica gel is used as a filler, the particle size of the filler is 3 μm, and the sample injection volume is 10-20 μl.
  3. 3. The method for detecting impurities in domperidone according to claim 1, wherein in the step (3), the flow rate is 1.5ml/min, the column temperature is 50 ℃, and the detection wavelength is 280nm.
  4. 4. The method of claim 1, wherein in the step (3), the impurities are impurity H, impurity I and/or impurity J.
  5. 5. The method for detecting impurities in domperidone according to claim 5, wherein the concentration of the impurity H is 1.255ng, 0.0004% and 0.3765ng, the concentration of the impurity I is 0.0034% and 3.43ng, the concentration of the impurity J is 0.001% and 1.16ng, 0.0006% and 0.0579ng, respectively.
  6. 6. The method for detecting impurities in domperidone according to claim 4 or 5, wherein the impurities in the step (3) further comprise impurity A, impurity B, impurity C, impurity D, impurity E and/or impurity F.
  7. 7. The method of claim 6, wherein in step (3), the retention time of each impurity is as follows: Impurity name Retention time (min) Impurity I 1.107 Impurity A 2.278 Impurity J 2.839 Impurity B 3.414 Impurity C 3.960 Impurity H 5.132 Impurity G 4.520 Impurity D+E 8.241 Impurity F 8.160 。
  8. 8. Use of the method for detecting impurities in domperidone according to any one of claims 1 to 5 for separating impurities in domperidone, detecting impurity species of domperidone and/or determining impurity content of domperidone.
  9. 9. The method of claim 8, wherein the impurity is impurity H, impurity I and/or impurity J.
  10. 10. The method of claim 8, wherein the impurities further comprise impurity A, impurity B, impurity C, impurity D, impurity E, and/or impurity F.

Description

Domperidone impurity detection method Technical Field The invention belongs to the field of pharmaceutical preparations, and particularly relates to a domperidone impurity detection method. Background Domperidone is a peripheral dopamine receptor antagonist mainly used for promoting gastric motility, relieving dyspepsia, nausea and vomiting, and the chemical purity and impurity spectrum of domperidone are critical to safety and effectiveness, and are also key to ensuring the safety and effectiveness of clinical medication. At present, an HPLC method is mainly adopted for detecting the domperidone impurities, for example, the invention patent with the application number of 202211464369.9 is a detection method of related substances in domperidone tablets, wherein a high performance liquid chromatography method is adopted, and all known impurities (impurities A, B, C, D, E, F and G) in the domperidone tablets can be completely separated, so that the separation degree among all spectral peaks is high, and the content of all impurities can be accurately detected. However, various impurities, such as impurity H, impurity I and impurity J, are also produced during the preparation of domperidone and the production of tablets, and the detection of these impurities is difficult to achieve by the above detection method. Disclosure of Invention The invention provides a domperidone impurity detection method, which can effectively separate impurities H, I and J in domperidone, can separate the impurities from the currently known impurities at one time, and realizes accurate monitoring of the content of each impurity. The technical scheme of the invention is realized as follows: The domperidone impurity detection method comprises the following steps: (1) Preparation of test solutions Taking domperidone to be detected, dissolving the domperidone with N, N-dimethylformamide and diluting the domperidone to be detected to prepare a test solution; (2) Assay Precisely measuring the solution to be tested, injecting the solution into a high performance liquid chromatograph, taking 0.5% ammonium acetate solution as a mobile phase A and methanol as a mobile phase B, performing gradient elution at a flow rate of 1.0-1.5ml/min and a column temperature of 30-50 ℃ to separate domperidone from impurities, detecting the separated impurities and obtaining a chromatogram, wherein the gradient elution procedure is as follows: 。 further, in the step (1), the domperidone to be tested is dissolved and diluted with N, N-dimethylformamide to prepare a solution containing 10mg per 1 ml. In the step (2), the chromatographic column is Hypersil BDS C18, the inner diameter of the chromatographic column is 4.6mm, the length of the chromatographic column is 100mm, octadecylsilane chemically bonded silica is used as a filler, the particle size of the filler is 3 mu m, and the sample injection volume is 10-20 mu l. Further, in the step (3), the flow rate was 1.5ml/min, the column temperature was 50℃and the detection wavelength was 280nm. Further, in the step (3), the impurities are impurities H, I and/or J. Further, the mass H corresponds to the concentration of the sample to be quantitatively detected at 0.0013%, the limit of the mass H is 1.255ng, the limit of the mass H corresponds to 0.0004% and is 0.3765ng, the impurity I corresponds to the concentration of the sample to be quantitatively detected at 0.0034%, the limit of the mass H is 3.43ng, the impurity J corresponds to the concentration of the sample to be quantitatively detected at 0.001%, the limit of the mass H is 1.16ng, the limit of the mass H corresponds to 0.0006% and is 0.0579ng. Further, in the step (3), the impurities further comprise an impurity A, an impurity B, an impurity C, an impurity D, an impurity E and/or an impurity F. Further, in the step (3), the retention time of each impurity is as follows: 。 the method for detecting the impurity in the domperidone is applied to separating the impurity in the domperidone, detecting the impurity type of the domperidone and/or determining the impurity content of the domperidone. Further, the impurities are impurities H, I and/or J. Further, the impurities further comprise an impurity A, an impurity B, an impurity C, an impurity D, an impurity E and/or an impurity F. The beneficial effects are that: The domperidone impurity detection method provided by the invention can detect the impurity A, the impurity B, the impurity C, the impurity D+E, the impurity F, the impurity H, the impurity I and the impurity J in domperidone, has high peak separation degree of each impurity, and can simultaneously detect the content of each impurity. The detection method provided by the invention has the advantages of good specificity, high sensitivity, good linearity, repeatability, solution stability, accuracy investigation and other experimental verification results. The result provides a new method for impurity separation, impurity type detection and impurit