Impurity detection method for pimobendan soft chewing dosage form

A technology of pimobendan and a detection method, applied in the field of impurity detection, can solve problems such as poor solubility, baseline fluctuation, poor compatibility, etc., and achieve the effects of prolonging service life, increasing durability, and increasing durability.

Pending Publication Date: 2021-12-17
BEIJING OUBOFANG MEDICAL TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] 1. The mobile phase pH of the prior art is 2.5. Under this mobile phase pH, the peaks of pimobendan impurities and excipients in the soft chewable dosage form cannot be completely separated, and the pH tolerance range of conventional chromatographic columns is 2-8. The pH of the mobile phase will greatly affect the service life of the column
[0018] 2. The existing technology is a two-phase gradient elution. For the impurity detection of pimobendan soft chews, the two-phase gradient elution cannot separate the excipients from the impurities and the main peak, and cannot achieve accurate detection of impurities
[0019] 3. Under the existing technical conditions, the main peak of pimobendan peaks at the place where the gradient of the mobile phase changes sharply. The sharp change of the mobile phase gradient will cause obvious fluctuations in the baseline. The peak at this place will affect the impurities before and after the main peak. In the detection situation, the impurities before and after the main peak will be indistinguishable from the baseline fluctuations, which will affect the detection sensitivity and impurity detection.
[0020] 4. The mobile phase system of the prior art is phosphate-acetonitrile, and wherein phosphate is mainly potassium salt, and potassium salt has an obvious effect on improving the tailing of basic compounds. Although pimobendan is a basic compound, due to its The solubility is poor, and an appropriate co-solvent or surfactant is usually added to soft chews to increase its solubility, and potassium salt and some surfactants have poor compatibility, so when the sample is eluted with potassium salt as mobile phase, it will be greatly Affect the life of the column
[0021] 5. For a dosage form with a complex matrix such as soft chews, the peaks of excipients usually have ultraviolet absorption. The existing technology cannot completely separate the peaks of excipients from impurities and the main peak, and thus cannot realize the detection of impurities. This is the prior art biggest disadvantage

Method used

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  • Impurity detection method for pimobendan soft chewing dosage form
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  • Impurity detection method for pimobendan soft chewing dosage form

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Adjusting the ratio of chromatographic column and mobile phase on the basis of EP method

[0063] Chromatographic conditions: Agilent C18 chromatographic column (4.6*250mm, 5μm); mobile phase A: 3g / L potassium dihydrogen phosphate solution (phosphoric acid to adjust the pH to 2.5), mobile phase B: acetonitrile; detection wavelength: 290nm, flow rate 1.0ml / min; Column temperature: 45°C;

[0064] time (min) mobile phase A mobile phase B 0.00 85 15 10.00 80 20 30.00 40 60 30.01 85 15 40.00 85 15

[0065] Test results such as image 3 As shown, under the conditions of Example 1, the auxiliary materials interfered with the main peak and the detection of impurities at 13min and 17min respectively.

Embodiment 2

[0067] Chromatographic conditions: on the basis of Example 1, the pH of the mobile phase A was adjusted to pH 3.0, and the chromatographic column was Agilent C18 (4.6*150mm, 4 μm).

[0068] Its test results are as Figure 4 As shown, under the conditions of Example 2, the peak eruption time of the main peak is about 15 minutes, but the auxiliary materials still interfere with the detection of the main peak and impurities.

Embodiment 3

[0070] Observe the experimental results by adjusting the mobile phase ratio

[0071] Chromatographic conditions: Agilent C18 column (4.6*150mm, 4μm), mobile phase A: 3g / L potassium dihydrogen phosphate solution (phosphoric acid to adjust pH to 3.0), mobile phase B: acetonitrile; detection wavelength: 290nm, flow rate 1.0ml / min, column temperature: 45°C

[0072] time (min) mobile phase A mobile phase B 0.00 85 15 10.00 80 20 20.00 70 30 40.00 40 60 40.01 85 15 50.00 85 15

[0073] Its test results are as Figure 5 As shown, it can be seen that the gradient at 10-20min still needs to be improved.

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Abstract

The invention discloses an impurity detection method for a pimobendan soft chewing dosage form, which is characterized in that three-phase high performance liquid chromatography is used for determination, and the chromatographic conditions comprise that a chromatographic column is C18, 4.6 mm * 250 mm, 4 [mu] m; a mobile phase A is a 2.6 g / L sodium dihydrogen phosphate solution, and the pH is adjusted to 3.0 by phosphoric acid; a mobile phase B is acetonitrile-methanol in a ratio of 80: 20; the column temperature is 45 DEG C; the detection wavelength is 290 nm; and the flow velocity is 1.0 ml / min. The pimobendan soft chewing dosage form solution is measured under the liquid chromatogram condition, and the impurity condition is judged according to the main peak and the impurity peak. In addition, under the method, a preservative in the pimobendan soft chewing dosage form can be detected. By adjusting the mobile phase system and optimizing the mobile phase gradient, the main peak of pimobendan appears at the gradient change mitigation position, the auxiliary material is completely separated from the main peak and the impurity peak, the auxiliary material does not interfere with impurity detection, the specificity is high, the sensitivity is high, and the impurity response is high.

Description

technical field [0001] The invention relates to a method for detecting impurities in a pimobendan soft chewing dosage form, and belongs to the technical field of drug detection. Background technique [0002] Heart disease is one of the most common aging diseases in dogs and cats. Pimobendan is a derivative of benzimidazole-pyridazinone. Heart failure is superior to conventional drugs, and has good safety and tolerance, can significantly improve the quality of life and quality of life of dogs, and has become a widely used drug for the treatment of heart failure in clinical practice. The drug compliance of sick animals is poor, and the soft chewable dosage form can greatly improve this problem. Therefore, the soft chewable dosage form of pimobendan is a research hotspot now, but the soft chewable dosage form has a complex matrix and contains more flavoring agents, which will affect the main components. Stability is greatly affected. [0003] The safety and effectiveness of d...

Claims

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Application Information

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IPC IPC(8): G01N30/02G01N30/06G01N30/34G01N30/36G01N30/74
CPCG01N30/02G01N30/06G01N30/34G01N30/36G01N30/74
Inventor 高腾周晶朱敏王松崔海峰
Owner BEIJING OUBOFANG MEDICAL TECH
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