Method for determining purity of daptomycin on basis of hydrogen nuclear magnetic resonance

A daptomycin and nuclear magnetic resonance technology, which is applied in the field of analysis, can solve the problems of determining the purity of daptomycin raw materials, affecting the purity measurement results, and greatly affecting the proportion, and can solve the problems of raw material drug purity determination and sample pretreatment. Simple, distraction-free effect

Inactive Publication Date: 2016-10-12
SHANDONG ANALYSIS & TEST CENT
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  • Abstract
  • Description
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AI Technical Summary

Problems solved by technology

The main deficiency of the above chromatographic method is: (1) ignore the possible solvent residues without ultraviolet absorption in the sample, such as water, ethanol, acetonitrile, etc., the chromatographic method content determination result may not be the true purity of daptomycin, still need to combine Gas chromatography and other methods deduct solvent residues; (2) peak shape and peak eluting time are greatly affected by the proportion of buffer salt in the aqueous phase, which in turn affects the purity measurement results; (3) high-purity daptomycin is required for quantification. Reference substance; (4) The analysis time is longer
[0006] Proton NMR method has been widely used in structural analysis and qualitative analysis of organic compounds due to its high sensitivity, high accuracy, and rapid analysis. , because there are many parameters that affect the measurement accuracy, and there is no clear rule to follow, and because of the differences in the structure and properties of the compounds, it is very difficult to construct a system based on the hydrogen nuclear magnetic resonance method to accurately determine the purity of compounds
At present, there is no report on the determination of the purity of daptomycin API based on proton nuclear magnetic resonance

Method used

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  • Method for determining purity of daptomycin on basis of hydrogen nuclear magnetic resonance
  • Method for determining purity of daptomycin on basis of hydrogen nuclear magnetic resonance
  • Method for determining purity of daptomycin on basis of hydrogen nuclear magnetic resonance

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Experimental program
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Effect test

Embodiment 1

[0039] Precisely weigh 10.260 mg of daptomycin sample and 2.037 mg of maleic acid, and add 600 μL and 250 μL of DMSO-d respectively. 6 After dissolving, transfer 480 μL of daptomycin solution and 20 μL of maleic acid solution to NMR tubes, and carry out 1 HNMR test. The resonant frequency of NMR spectrometer is 400MHz, 90°pulse, d 1 is 100s, the number of sampling accumulations is 64, the spectral width is 20ppm, the test temperature is 23°C, and the AQ is 4.1s.

[0040] Such as figure 1 shown in 1 In the H NMR spectrum, the internal standard maleic acid δ H 6.02 Signal peak integral value is 1, daptomycin δ H The integral value of the signal at 6.53 was 1.68. According to formula-1, the purity of daptomycin was calculated to be 92.2%, repeated 6 times, the standard error = 0.18%, and the relative standard deviation was 0.2%.

Embodiment 2

[0042] 1 The H NMR test sample is the same as in Example 1. The resonant frequency of NMR spectrometer is 400MHz, 90°pulse, d 1 is 50s, the number of sampling accumulations is 64, the spectral width is 20ppm, the test temperature is 23°C, and the AQ is 4.1s.

[0043] Such as figure 2 shown in 1 In the H NMR spectrum, the internal standard maleic acid δ H 6.02 Signal peak integral value is 1, daptomycin δ H The integral value of the signal at 6.53 was 1.69. According to formula-1, the purity of daptomycin was calculated to be 92.8%, repeated 6 times, standard error = 0.25%, relative standard deviation 0.1%.

Embodiment 3

[0045] 1 The H NMR test sample is the same as in Example 1. The resonant frequency of NMR spectrometer is 400MHz, 90°pulse, d 1 The time is 13s, the number of sampling accumulations is 32, the spectrum width is 20ppm, the test temperature is 23°C, and the AQ is 4.1s.

[0046] Such as image 3 shown in 1 In the H NMR spectrum, the internal standard maleic acid δ H 6.02 Signal peak integral value is 1, daptomycin δ H The integral value of the signal at 6.53 was 1.75. According to formula-1, the purity of daptomycin was calculated to be 96.1%, repeated 6 times, standard error = 0.2%, and relative standard deviation 0.2%.

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Abstract

The invention discloses a method for determining the purity of daptomycin on the basis of hydrogen nuclear magnetic resonance. The method comprises the following steps that 1, longitudinal relaxation time (T<1>) of quantitative target peaks of daptomycin and an internal standard substance in a deuterated reagent is determined; 2, a flip angle of a nuclear magnetic resonance wave spectrometer and relaxation delay time (d<1>) are set according to the determined T<1> value; 3, integral areas of all quantitative target peaks of a daptomycin sample and the internal standard substance are determined according to the parameters set in the second step, and the molar mass ratio of daptomycin to the internal standard substance is obtained; 4, the purity of daptomycin is calculated according to the mass of the internal standard substance, and the purity of daptomycin is calculated according to the following formula of W%=(m<IS> *H<IS>*A<S>*M<S>*100%) / (M<IS>*A<IS>*m<S>*H<S>). The method has the advantages of being good in repeatability and easy and convenient to operate, can rapidly and accurately detect the purity of daptomycin and provides a novel method for strictly controlling the purity of daptomycin.

Description

technical field [0001] The invention belongs to the technical field of analysis, and in particular relates to a method for measuring the purity of daptomycin based on hydrogen nuclear magnetic resonance. Background technique [0002] Daptomycin is a cyclic lipopeptide antibiotic produced by Streptomyces roseospora, which has a novel chemical structure as follows: [0003] [0004] It mainly kills bacteria by disrupting the transport of amino acids in the cell membrane and hindering the synthesis of peptidoglycan on the bacterial cell wall. In addition to its strong bactericidal effect on Gram-positive bacteria, daptomycin also has strong activity on strains that have shown resistance to axicillin, vancomycin and linezolid. In addition, its characteristics of less toxic side effects, mild adverse reactions, and low treatment costs make it a hot spot for research and development by domestic and foreign pharmaceutical companies. [0005] At present, the method for analyzin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N24/08
CPCG01N24/08
Inventor 王志伟魏祥玉闫慧娇林云良李锋赵汝松陈跃高红梅
Owner SHANDONG ANALYSIS & TEST CENT
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