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Method for rapidly measuring purity of pregabalin bulk drug based on H-nuclear magnetic resonance (HNMR)

A technology of pregabalin and nuclear magnetic resonance, which is applied in the field of medical analysis, can solve problems such as the accuracy of proton nuclear magnetic quantitative method to be discussed, the determination of the purity of pregabalin raw materials, and the impact on the accuracy of final quantitative results, etc., to achieve convenient content analysis and Effects of quality control, ensuring accuracy, and reducing analysis costs

Inactive Publication Date: 2016-10-26
SHANDONG ANALYSIS & TEST CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Pulse dump angle and relaxation delay time (d 1 ) are two important instrument parameters, which directly affect the accuracy of the final quantitative results, but are often neglected in the application of pharmaceutical analysis in the early stage. Therefore, the accuracy of the established proton nuclear magnetic quantitative method is open to question
[0005] Proton NMR has been widely used in the 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 pregabalin raw material based on proton magnetic resonance method

Method used

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  • Method for rapidly measuring purity of pregabalin bulk drug based on H-nuclear magnetic resonance (HNMR)
  • Method for rapidly measuring purity of pregabalin bulk drug based on H-nuclear magnetic resonance (HNMR)
  • Method for rapidly measuring purity of pregabalin bulk drug based on H-nuclear magnetic resonance (HNMR)

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Accurately weigh 6.262 mg of pregabalin sample and 5.964 mg of maleic acid, dissolve them in 500 μL of heavy water, transfer them to NMR tubes, and carry out 1 H NMR test. The resonant frequency of NMR spectrometer is 400MHz, 90°pulse, d 1 is 50s, the number of sampling accumulations is 16, the spectral width is 20ppm, the test temperature is 23°C, and the AQ is 4.1s.

[0044] like figure 1 shown in 1 In the H NMR spectrum, the internal standard maleic acid δ H 6.23 Signal peak integral value is 1, pregabalin δ H The integral value of the signal at 1.13 was 0.748. According to formula-1, the purity of pregabalin could be calculated to be 96.7%. Repeated 6 times, the standard error was 0.16%, and the relative standard deviation was 0.1%.

[0045] W%=(m IS ×H IS ×A S × M S ×100%) / (M IS ×A IS ×H S × m S ) (Formula 1)

[0046] W% - the purity of pregabalin

[0047] m IS - the quality of the internal standard, 5.904mg

[0048] h IS - the number of protons...

Embodiment 2

[0056] 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 40s, the number of sampling accumulations is 16, the spectral width is 20ppm, the test temperature is 23°C, and the AQ is 4.1s.

[0057] like figure 2 shown in 1 In the H NMR spectrum, the internal standard maleic acid δ H 6.23 Signal peak integral value is 1, pregabalin δ H The integral value of the signal at 1.13 is 0.754, and the purity of pregabalin can be calculated according to formula-1 to be 97.5%, repeated 6 times, the standard error = 0.20%, and the relative standard deviation is 0.2%.

Embodiment 3

[0059] 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 30s, the number of sampling accumulations is 16, the spectral width is 20ppm, the test temperature is 23°C, and the AQ is 4.1s.

[0060] like image 3 shown in 1 In the H NMR spectrum, the internal standard maleic acid δ H 6.23 Signal peak integral value is 1, pregabalin δ H The integral value of the signal at 1.13 was 0.754. According to formula-1, the purity of pregabalin could be calculated to be 97.5%. Repeated 6 times, the standard error was 0.11%, and the relative standard deviation was 0.3%.

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Abstract

The invention discloses a method for rapidly measuring the purity of a pregabalin bulk drug based on H-nuclear magnetic resonance (HNMR). The method comprises the following steps: (1) measuring the vertical relaxation time (T1) of pregabalin and internal standard substance quantitative target peak in a deuterated reagent; (2) according to the measured T1 value, setting the flip angle and relaxation retard time (d1) of a nuclear magnetic resonance spectrometer, wherein the flip angle is 30 to 90 degrees, and the relaxation retard time (d1) >=(7 / 3*T1max~5*T1max); (3) according the parameters set in the step (2), measuring the integral areas of each quantitative target peaks of the pregabalin sample and the internal standard substance to obtain the mole ratio of pregabalin to the internal standard substance; (4) according to the mass of the internal standard substance, calculating the mass of pregabalin, and finally calculating the purity of pregabalin by the following formula: W%=(mIS*HIS*AS*MS*100%) / (MIS*AIS*HS*mS). The method has the advantages of accuracy, stability, and fastness.

Description

technical field [0001] The invention belongs to the technical field of medical analysis, and in particular relates to a method for rapidly measuring the purity of pregabalin crude drug based on proton nuclear magnetic resonance. Background technique [0002] Pregabalin (Pregabalin) is a gamma-aminobutyric acid (GABA) receptor antagonist developed by Pfizer of the United States, which is a 3-alkyl substitution of GABA. Clinically, it is mainly used for the treatment of peripheral neuralgia, anticonvulsant and auxiliary treatment of partial epileptic seizures. Compared with its similar drug, gabapentin, it has the advantages of low dose, less toxic and side effects, etc., and its dosage forms are mainly tablets and capsules. This variety has a good market prospect and has been widely concerned by domestic and foreign pharmaceutical research and development enterprises. [0003] Pregabalin is a saturated hydrocarbon compound with no conjugated structure in the molecule, and i...

Claims

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Application Information

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IPC IPC(8): G01N24/08
CPCG01N24/082
Inventor 王志伟李锋魏祥玉林玉良赵汝松闫慧娇陈跃高红梅
Owner SHANDONG ANALYSIS & TEST CENT
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