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A method for determining biapenem and/or related substances by high performance liquid chromatography

A high-performance liquid chromatography and biapenem technology, applied in the field of pharmaceutical analysis, can solve the problems of inaccurate detection data, unstable baseline, downward drifting trend, etc., and achieve accurate detection results, good main peak shape, excellent weight present effect

Active Publication Date: 2022-02-08
SHENZHEN HAIBIN PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] However, the two methods disclosed above all adopt isocratic elution, and its disadvantages are: 1) some impurities will remain in the chromatographic column, which will affect the accuracy of the detection results and reduce the service life of the chromatographic column; 2) the impurity peak Good baseline separation from impurity peaks cannot be achieved, resulting in inaccurate detection results; 3) The content of related substances and polymer impurities in biapenem cannot be detected at the same time
[0010] Although this method uses gradient elution, there are still the following shortcomings: 1) the baseline is not stable, and there is an obvious downward drift trend, which leads to inaccurate detection data and affects the accuracy of the detection results; 2) the method is not applicable Determination of related substances in biapenem
[0011] Therefore, in the method disclosed in the prior art for the determination of biapenem and / or related substances by high performance liquid chromatography, some impurities cannot be detected, good baseline separation cannot be achieved between impurity peaks and impurity peaks, and the detection results are inconsistent. accurate defect
In addition, there is a lack of methods in the art that can simultaneously detect the content of related substances and polymer impurities in biapenem drugs

Method used

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  • A method for determining biapenem and/or related substances by high performance liquid chromatography
  • A method for determining biapenem and/or related substances by high performance liquid chromatography
  • A method for determining biapenem and/or related substances by high performance liquid chromatography

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0089] Example 1 Type of buffer salt - selection of elution ratio

[0090] This example examines the impact of different buffer salt types-elution ratios on the detection of crude apenem and related substances

[0091] 1.1 Dipotassium hydrogen phosphate-methanol

[0092] With reference to the method described in the Chinese invention patent whose publication number is CN 105277630A:

[0093]Chromatographic column: C18 column (4.6mm×250mm, 5μm); column temperature: 35°C; mobile phase: 0.05mol / L dipotassium hydrogen phosphate solution (phosphoric acid to adjust pH=5.6): methanol volume ratio is 97:3; flow rate: 1.0ml / min, detection wavelength: 220nm; isocratic elution procedure, see the detection results Figure 1A and Table 3.

[0094] 1.2 Sodium acetate-acetonitrile

[0095] With reference to Zhang Jing, Xing Liangbin, Chinese Journal of Antibiotics, Volume 31, No. 9, September 2006, p565-566, the method:

[0096] Chromatographic column: C18 column (4.6mm×250mm, 5μm), c...

Embodiment 2

[0109] Example 2 Verification of buffer salt type

[0110] In order to eliminate the influence of the mobile phase elution ratio on the separation effect, the gradient elution was uniformly carried out according to Table 2, and the detection effect of different buffer salts compared with apenem and related substances was investigated.

[0111] Choose octadecylsilane bonded silica gel column Ultimate AQ-C18 (4.6mm×250mm, 5μm), use KOH or phosphoric acid to adjust pH=6.5 with 0.01mol / L sodium acetate, ammonium acetate, sodium salt of phosphoric acid or Potassium salt buffer solution was used as mobile phase A, and acetonitrile was used as mobile phase B, and gradient elution was performed according to Table 2; column temperature: 35°C, flow rate: 0.8ml / min, detection wavelength: 220nm.

[0112] Experimental results: see figure 2 and Table 4.

[0113] Table 4 Effect of different phosphates on chromatographic behavior

[0114]

[0115] It can be seen from the experimental...

Embodiment 3

[0116] Example 3 Choice of buffer salt pH

[0117] 3.1 Test object

[0118] Prepare a 0.01mol / L potassium dihydrogen phosphate buffer solution, and use phosphoric acid or potassium hydroxide to adjust the pH value to 3.0, 4.0, 4.7, 5.0, 5.6, 6.0, 6.5, 7.0, and 8.0 as mobile phase A.

[0119] 3.2 Experimental method

[0120] Chromatographic column: Octadecylsilane bonded silica gel column ZORBAX SB-C18 (4.6mm×250mm, 5μm);

[0121] The potassium dihydrogen phosphate buffer solution at each pH value mentioned above was used as the mobile phase A, and acetonitrile was used as the mobile phase B liquid; the gradient elution program shown in Table 5 was adopted. Column temperature: 35°C, flow rate: 0.8ml / min, detection wavelength: 220nm.

[0122] Table 5 Gradient elution program

[0123] t(min) 0 10 25 45 A (volume: %) 100 100 90 10 B (volume: %) 0 0 10 90

[0124] Preparation of test solution:

[0125] Biapenem test product solution: Accur...

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Abstract

The invention provides a method for determining the content of biapenem and / or related substances by high performance liquid chromatography, the method adopts a system composed of liquid A and liquid B for gradient elution, wherein the liquid A is phosphoric acid Saline solution, liquid B is acetonitrile or methanol - acetonitrile mixed solution. Compared with the prior art, the method of the present invention can separate and detect as many impurities as possible while achieving baseline separation of biapenem and impurities, or impurities. The measurement result obtained by the method of the invention is accurate, and the content of biapenem-related substances and polymer impurities can be simultaneously determined. In addition, the method of the present invention has excellent batch-to-batch and column-to-column reproducibility, and is suitable for industrial production.

Description

technical field [0001] The invention relates to the field of drug analysis, in particular to a method for determining biapenem and / or related substances by using high performance liquid chromatography. Background technique [0002] Biapenem (Biapenem) is a 1-β-methyl carbapenem antibiotic with broad-spectrum antibacterial activity jointly developed by Japan Lederle Company and American Cyamide Company. Biapenem was approved for marketing in Japan in 2002. The trade name is "Omegacin" and the chemical name is (1R,5S,6S)-2-[(6,7-dihydro-5H-pyrazol[1,2- a][1,2,4]-Triazolium-6-yl)thio]-6-[(R)-1-hydroxyethyl]-1-methylcarbapenem-2-ene-3- Carboxylate, structure as shown in (I): [0003] [0004] Related substances (also known as impurities) mainly refer to starting materials, intermediates, polymers, side reaction products, and degradation products during storage brought in during the production process. However, impurities such as ring-opening degradation products, acid hydr...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): G01N30/02
Inventor 何秀红谭高玲王涛罗文军张验军邓鹿江任鹏
Owner SHENZHEN HAIBIN PHARMA
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