Method for analyzing milrinone related substances by high performance liquid chromatography

A technology for high performance liquid chromatography and related substances, which is applied in the field of analyzing milrinone related substances, can solve the problems such as the need for further improvement of quality control, the limited detection ability of impurities, etc. Effect

Active Publication Date: 2019-08-06
SHANGHAI XUDONG HAIPU PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The above two methods have limited ability to detect impurities, and the quality control of products needs to be further improved.

Method used

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  • Method for analyzing milrinone related substances by high performance liquid chromatography
  • Method for analyzing milrinone related substances by high performance liquid chromatography
  • Method for analyzing milrinone related substances by high performance liquid chromatography

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Embodiment 1 Analytical method is established

[0036] Instrument: Agilent 1100 / 1260 HPLC

[0037] Column: Agilent ZORBAX SB-C 8 (250×4.6mm, 5μm)

[0038] Mobile phase A: Dipotassium hydrogen phosphate solution at pH 7.5 (take 2.7g of dipotassium hydrogen phosphate, add 800ml of water to dissolve, add 2.4ml of triethylamine, adjust the pH value to 7.5 with phosphoric acid)

[0039] Mobile phase B: water-acetonitrile (50:50)

[0040] The flow rate is 1ml / min; the column temperature is 30°C; the detection wavelength is 260nm; the injection volume is 20μl.

[0041] The elution procedure is shown in Table 2, and the obtained spectrum can be found in figure 1 , Realized the characterization of impurities in 13, wherein 4 kinds of impurities are non-critical impurities of this product, which are not included in the method of this embodiment, but this method can still effectively detect the impurities that are not reflected.

[0042] Table 2

[0043]

[0044] System s...

Embodiment 2

[0052] Embodiment 2 durability test

[0053] Fine-tune the temperature (±5°C), flow rate (±20%), detection wavelength (±2nm), mobile phase ratio, and initial gradient ratio to evaluate the tolerance of the measurement results without being affected by small changes in the parameters of the measurement conditions. The test results are shown in Table 4.

[0054] Table 4

[0055]

[0056]

[0057] It can be seen from Table 4 that the detection method of milrinone-related substances can meet the system applicability requirements by adjusting the column temperature, flow rate, initial mobile phase ratio, and detection wavelength, indicating that the method has good durability.

Embodiment 3

[0058] Embodiment 3 detection limit

[0059] For known impurities: prepare a solution with a concentration of 0.025% of the test substance (at least half of the impurity limit concentration), if the signal-to-noise ratio S / N is not less than 10, then use the concentration of 0.025% of the test substance as the limit of quantification; For a solution with a concentration of 0.01% of the test substance, if the signal-to-noise ratio S / N is not less than 2, then the concentration of 0.01% of the test substance is the detection limit concentration;

[0060] For unknown impurities: replace the quantification limit concentration and detection limit concentration of a single unknown impurity with principal components.

[0061] After testing, the detection limit concentration of impurity U, impurity B, impurity H, impurity A, impurity S, milrinone, impurity D, impurity T, impurity C and impurity W were 0.2022 μg / ml, 0.2010 μg / ml, 0.2237 μg / ml, 0.1984 μg / ml, 0.1981 μg / ml, 0.2037 μg / ml,...

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Abstract

The invention discloses a method for analyzing milrinone related substances by high performance liquid chromatography. The method is characterized by adopting a C18 reversed phase chromatographic column, regarding a dipotassium phosphate solution with a pH value ranging from 6.5 to 8.5 as a mobile phase A and regarding water/acetonitrile with a volume ratio of 30:70-60:40 as a mobile phase B for implementing elution, so as to realize detection of milrinog and its 16 kinds of impurities by one sample loading. Compared with the prior art, the method provided by the invention can detect more impurities, and has good sensitivity to the impurities. In the specific application, the method formulates limits of the key impurities according to test results of batches of samples, thereby greatly improving the economic applicability in the actual production process.

Description

technical field [0001] The invention relates to a method for analyzing impurities involved in compound synthesis, in particular to a method for analyzing milrinone-related substances. Background technique [0002] Milrinone, the English name is Milrinone, the chemical name is 1,6-dihydro-2-methyl-6-oxo-[3,4'bipyridine]-5-carbonitrile, and the molecular formula is C 12 h 9 N 3 O, the molecular weight is 211.22, the CAS number is 78415-72-2, and the structural formula is as follows: [0003] [0004] In the manufacture of potent active molecules for pharmaceutical products, impurities are critical quality attributes that affect the product. The structure, physical and chemical properties and toxicity of impurities are complex, so the inspection and research of related substances is often one of the difficulties in drug development. In addition to being related to the pharmacological activity of the main component, the adverse reactions of drugs during clinical use are a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/88
CPCG01N30/88G01N2030/884
Inventor 杨易可孙燕红赵文芳孙晔陈小林梁屹张帆
Owner SHANGHAI XUDONG HAIPU PHARMA
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