A kind of ultra high performance liquid chromatography analysis method of semaglutide

An ultra-high performance liquid chromatography and chromatographic analysis technology, applied in the field of peptide quality analysis, can solve the problems of unclear toxicological data, affecting the product quality of semaglutide, and the risk of patients' medication, increasing the number of impurities and improving the permeability. , the effect of increasing the number of impurities

Active Publication Date: 2022-03-25
浙江湃肽生物股份有限公司南京分公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] During the synthesis and storage of semaglutide, a series of process impurities and degradation impurities are inevitably produced, such as isomer impurities, defective peptide impurities, etc. These impurities are collectively referred to as related substances, and their existence seriously affects the quality of semaglutide. The quality of the product, and the toxicological data of these impurities are not yet clear, there must be potential risks for patients
At present, there are few quality analysis methods for semaglutide in the market. In order to monitor the product quality of semaglutide and improve drug safety and stability of patients, it is of great practical significance to develop a quality analysis method for semaglutide.

Method used

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  • A kind of ultra high performance liquid chromatography analysis method of semaglutide
  • A kind of ultra high performance liquid chromatography analysis method of semaglutide
  • A kind of ultra high performance liquid chromatography analysis method of semaglutide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Preparation of core-shell fillers:

[0054] Preparation and Surface Modification of Non-porous Silica Microspheres

[0055] Mix absolute ethanol, deionized water, and ammonia water at a volume ratio of 15:0.7:1, and ultrasonically disperse for 12 minutes to obtain liquid A; take tetraethyl orthosilicate and add it to absolute ethanol at a volume ratio of 1:8 Make a dilute solution, sonicate for 15 minutes to obtain liquid B; slowly add liquid B to liquid A, the volume ratio of liquid A and liquid B is 2.1:1, add dropwise in 15 hours, then react at room temperature for 4 hours; remove by centrifugation Alkaline solution, deionized water, vacuum filtration and washing until the filtrate is neutral, then washing with ethanol 4 times, and vacuum drying at 65 °C for 8 h to obtain non-porous silica microspheres;

[0056] Disperse non-porous silica microspheres in absolute ethanol at a concentration of 0.02 g / mL, add γ-ureapropyltrimethoxysilane, in which non-porous silica mi...

Embodiment 2

[0062] The difference between the preparation of core-shell type filler and embodiment 1 is:

[0063] Core-shell SiO 2 During the preparation of microspheres, the mass ratio of surface-modified non-porous silica microspheres to urea was 1:1.1; the solid-liquid ratio of modified non-porous silica microspheres to silica sol solution was 1 g:1.6 mL ; The solid-liquid ratio of modified non-porous silica microspheres to formaldehyde solution was 1 g: 1.2 mL; the mass ratio of 2-aminopyrimidine-5-formaldehyde hydrate to urea was 1: 1.7.

[0064] Core-shell SiO 2 During the bonding process on the surface of microspheres, core-shell SiO 2 The mass ratio of microspheres and octadecyltrichlorosilane is 1:1.15.

Embodiment 3

[0066] The difference between the preparation of the core-shell filler and Example 1 is that the core-shell SiO 2 During the preparation of the microspheres and the surface bonding process, a new type of organosilane is added, specifically:

[0067] core-shell SiO 2 The microspheres were added to hydrochloric acid solution (hydrochloric acid / water = 1, v / v) with a concentration of 20 g / mL, stirred and activated in an oil bath at 138 °C for 7 h after ultrasonication for 8 min, and then deionized water was filtered and washed until neutral , dried in vacuum at 120 °C for 10 h; then added the dried toluene (core-shell SiO 2 The solid-to-liquid ratio of microspheres to toluene was 1 g: 30 mL), after ultrasonic dispersion for 6 min, octadecyltrichlorosilane (core-shell SiO 2 The mass ratio of microspheres, octadecyltrichlorosilane is 1:1.24) and new organosilanes (with core-shell SiO 2 The mass ratio of the microspheres was 1:0.42), stirred and refluxed for 22 h in an oil bath a...

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Abstract

The invention discloses an ultra-high performance liquid chromatography analysis method for semaglutide, which relates to the technical field of polypeptide quality analysis, including: the chromatographic column filler in ultra-high performance liquid chromatography includes a core-shell filler, which is a surface-bonded Core-shell SiO 2 Microspheres; the above-mentioned compound for surface bonding includes at least octadecyltrichlorosilane; the pore diameter of the above-mentioned chromatographic column packing is 16-20 nm; the above-mentioned surface-bonded core-shell SiO 2 Core-shell SiO in microspheres 2 The preparation method of the microspheres is a polymerization-induced colloid aggregation technology; the template used includes a new type of urea-formaldehyde resin, and its raw material components include urea, formaldehyde and 2-aminopyrimidine-5-formaldehyde hydrate. The ultra-high performance liquid chromatography analysis method provided by the present invention significantly improves the separation between semaglutide-related impurities and the main peak, significantly increases the number of detected impurities, and has more excellent peak shape and column efficiency, and can better Monitor the product quality of semaglutide.

Description

technical field [0001] The invention belongs to the technical field of polypeptide quality analysis, and in particular relates to an ultra-high performance liquid chromatography analysis method for semaglutide. Background technique [0002] Semaglutide, whose English name is Semaglutide, is a new type of long-acting glucagon-like peptide-1 (GLP-1) analogue developed and produced by Novo Nordisk, Denmark, for the treatment of type II diabetes. Semaglutide has the effects of lowering blood sugar, losing weight and protecting cardiovascular system, and was recommended by the FDA for approval on October 18, 2017. After the Lys side chain of semaglutide is modified by PEG, Glu and octadecanedicarboxylic acid, the hydrophilicity is greatly improved, and the binding force with albumin is enhanced; at the same time, after the Ala at the second position of the N-terminus is mutated into Aib, the effective It avoids being inactivated by DPP-IV enzymatic hydrolysis, and the half-life ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): G01N30/02G01N30/30G01N30/32G01N30/34G01N30/56G01N30/74
CPCG01N30/02G01N30/30G01N30/32G01N30/34G01N30/56G01N30/74G01N2030/324G01N2030/562
Inventor 张飞华叶有志汪岳斌马奔
Owner 浙江湃肽生物股份有限公司南京分公司
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