HPLC (High Performance Liquid Chromatography) test method for related substances in L-prolinamide

A technology related to substances, prolineamides, applied in the field of column chromatography testing or analyzing materials, can solve the problems of short retention time, ineffective detection, small response value, etc.

Pending Publication Date: 2022-06-21
ZHEJIANG GUOBANG PHARMA
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In the process of synthesizing the compound, the impurities that may be introduced mainly include L-proline, proline dimer, L-hydroxyproline, isomer D-proline amide, etc., isomer D-proline Aminoamide can be effectively detected by chiral chromatographic columns, while L-prolineamide and its impurities L-proline, proline di

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • HPLC (High Performance Liquid Chromatography) test method for related substances in L-prolinamide
  • HPLC (High Performance Liquid Chromatography) test method for related substances in L-prolinamide
  • HPLC (High Performance Liquid Chromatography) test method for related substances in L-prolinamide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] (1) Instruments and reagents

[0035] ① Instrument: High performance liquid chromatography, Agilent 1260; electronic balance, Mettler XSR 105; pH meter, Mettler FE28.

[0036] ②Reagents: sodium octanesulfonate (chromatographic grade), Scharlau; sodium dihydrogen phosphate dihydrate (analytical grade), Sinopharm Group; acetonitrile (chromatographic grade); phosphoric acid (analytical grade), Sinopharm Group.

[0037] ③Chromatographic conditions: chromatographic column Agilent TC-C18(2), 5μm; 4.6×250mm, flow rate 0.5ml / min; detection wavelength 200nm; injection volume 10μL; column temperature 30°C.

[0038] ④ Mobile phase: Weigh 5.13 g of sodium octane sulfonate and 1.48 g of sodium dihydrogen phosphate dihydrate, add 850 ml of water to dissolve, add 150 ml of acetonitrile and mix, and adjust the pH to 3.0 with phosphoric acid.

[0039] ⑤ Solvent: mobile phase.

[0040] (2) Preparation of each solvent

[0041] ① Each impurity positioning solution: Weigh the appropriate...

Embodiment 2

[0063] The chromatographic conditions in this example: the flow rate is 0.4 ml / min, and other chromatographic conditions are the same as those in Example 1.

[0064] Take 10 μL of the system suitability solution, inject it into the liquid chromatograph, and record the chromatogram.

[0065] The detection results of related substances in the system suitability solution are shown in Table 2, and the obtained HPLC chromatogram is shown in Table 2. Figure 7 , it can be seen from Table 2 that all impurity peaks are effectively separated, and the main peak is completely separated from the adjacent impurity peaks.

[0066] Table 2: System Suitability Solution Related Substance Test Results

[0067] Impurity name Retention time (min) degree of separation Number of theoretical plates L-Hydroxyproline 8.292 1.7 28718 L-Proline 9.665 1.96 17762 Proline dimer 11.089 4.96 23867 L-Prolineamide 28.625 16.4 17367

Embodiment 3

[0069] The chromatographic conditions in this example: the flow rate is 0.6 ml / min, and other chromatographic conditions are the same as those in Example 1.

[0070] Take 10 μL of the system suitability solution, inject it into the liquid chromatograph, and record the chromatogram.

[0071] The detection results of related substances in the system suitability solution are shown in Table 3, and the obtained HPLC chromatogram is shown in Table 3. Figure 8 , it can be seen from Table 3 that all impurity peaks are effectively separated, and the main peak is completely separated from the adjacent impurity peaks.

[0072] Table 3: System Suitability Solution Related Substance Test Results

[0073] Impurity name Retention time (min) degree of separation Number of theoretical plates L-Hydroxyproline 5.502 1.71 22619 L-Proline 6.407 1.91 18082 Proline dimer 7.384 5 21316 L-Prolineamide 18.907 16.96 18078

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Linearaaaaaaaaaa
Linearaaaaaaaaaa
The inside diameter ofaaaaaaaaaa
Login to view more

Abstract

The invention provides an HPLC (High Performance Liquid Chromatography) test method for related substances in L-prolinamide, and belongs to the technical field of column chromatography test or analysis materials. The L-prolinamide related substance is an impurity introduced or generated by degradation in a synthesis process of L-prolinamide, a mobile phase is a solution obtained by adding water to dissolve sodium octanesulfonate and sodium dihydrogen phosphate dihydrate and then adding acetonitrile to uniformly mix, a high performance liquid chromatography is adopted, octadecylsilane chemically bonded silica is used as a filler to perform chromatographic column separation, and the content of the L-prolinamide related substance is measured. The mobile phase is used as a solvent to perform isocratic elution on impurities. The method is applied to impurity determination of related substances of L-prolinamide, and has the advantages of being stable in chromatographic condition system, good in linearity, high in precision, high in chromatographic condition sensitivity, good in specificity, stable in determination solution within 35 hours and the like.

Description

technical field [0001] The application relates to an HPLC test method for related substances in L-prolineamide, and belongs to the technical field of column chromatography test or analysis materials. Background technique [0002] L-prolineamide is an important optically active pyrrole derivative and an important chiral intermediate of the hypoglycemic drug Vildagliptin. The molecular formula of L-prolineamide is C 5 H 10 N 2O The structural formula of is shown in formula (1): [0003] [0004] In the process of synthesizing this compound, the impurities that may be introduced are mainly L-proline, proline dimer, L-hydroxyproline, isomer D-prolineamide, etc. Aminoamide can be effectively detected by chiral chromatographic column, while L-prolineamide and impurities L-proline, proline dimer, L-hydroxyproline structure have no conjugated system, and the UV absorption is weak. The conventional HPLC reversed-phase chromatography analysis method detects that its retention ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): G01N30/02G01N30/30G01N30/32G01N30/34G01N30/74G01N30/86B01J20/281
CPCG01N30/02G01N30/30G01N30/32G01N30/34G01N30/74G01N30/8679G01N2030/027G01N2030/3007G01N2030/324G01N2030/342Y02P20/55
Inventor 胡德行吴娇王欢蔡一凡朱庆国李开莹王李洪秦欣荣姚礼高邱家军
Owner ZHEJIANG GUOBANG PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap