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GLP-1a
GLP-1 (glucagon-like peptide-1) is a naturally occurring peptide hormone released in the gut following a meal. It belongs to the group of incretins and helps to regulate blood glucose levels. When blood glucose levels are elevated, GLP-1 stimulates insulin secretion from the beta cells of the pancreas whilst simultaneously inhibiting the release of glucagon. This promotes the uptake of glucose into the body’s cells and reduces the release of glucose from the liver. In addition, GLP-1 delays gastric emptying and, via signals to the brain, influences feelings of hunger and satiety.
GLP-1 receptor agonists (GLP-1a for short), such as semaglutide and liraglutide, utilise this natural mechanism of action. The ‘a’ stands for agonists, i.e. active substances that activate the GLP-1 receptor and thereby mimic its effect. The abbreviation GLP-1-RA is also frequently used in scientific texts. They activate the GLP-1 receptor and have a longer duration of action than the body’s own hormone. Depending on the specific preparation, they are used to treat type 2 diabetes and for weight management in cases of obesity or excess weight with associated conditions. Their effect on blood sugar and appetite makes them an important class of active substances in the treatment of metabolic disorders.
Reliable analysis of GLP-1 and GLP-1 receptor agonists is crucial for the development and quality control of these peptide-based medicines. In addition to identity and active ingredient content, purity and stability must be assessed. During manufacture and storage, impurities, degradation products and aggregates may form, which can affect product quality. As many of these components are structurally very similar to the active substance itself, high-performance and selective chromatographic methods are required.
Technical Data
Reversed-phase HPLC (RP-HPLC) separates peptides and accompanying components on the basis of their differing interactions with a hydrophobic stationary phase. It is used in particular for quantification, purity testing and the analysis of manufacturing-related impurities and degradation products. Corresponding UHPLC methods can enable higher separation efficiency or shorter analysis times.
Size-exclusion chromatography (SEC) complements these analyses by separating molecules according to their hydrodynamic size. It is primarily used to detect high-molecular-weight components and aggregates. Under native conditions, non-covalent assemblies can also be investigated; denaturing conditions, on the other hand, facilitate the analysis of permanently bound aggregates, such as covalent aggregates.
For further characterisation, liquid chromatography is coupled with mass spectrometry. LC-MS and LC-MS/MS provide additional information on molecular mass and structure, thereby supporting identity verification as well as the identification of impurities and degradation products. The combination of suitable HPLC columns, separation conditions and detection methods thus enables a targeted investigation of the various quality attributes of GLP-1 active substances.
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Manufacturer Overview
Manufacturer: Shimadzu
| Separation technology | Product |
| HPLC – Reversed-phase |
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Manufacturer: ThermoFisher
| Separation Technology | Product range |
| UHPLC – Reversed Phase |
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- Thermo Hypersil Gold Peptide Hypersil Gold C4 Optimization of RPLC-UV methods for Impurity Analysis of the GLP-1a Semaglutide and Tirzepatide
- Thermo Hypersil Gold Peptide Stability-indicating HPLC-UV Method Development for GLP-1a Semaglutide
- Thermo Hypersil Gold Peptide Comprehensive LC-MS Characterization of the GLP-1a Semaglutide and Sample-related Impurities
- Thermo Hypersil Gold Peptide Confident and Sensitive Identification of Semaglutide Degradation Products and Impurities by UHPLC-HRAM MS
Manufacturer: Waters
| Separation Technology | Product range |
| UHPLC – Reversed Phase |
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| HPLC – Reversed-phase |
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| UHPLC – HILIC |
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| UHPLC – SEC |
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| Sample preparation |
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| Mobile phase |
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- Waters AccQ-Tag Ultra Rapid High-Throughput Amino Acid Analysis of GLP-1a
- Waters ACQUITY Premier Peptide BEH C18 CSH C18 Method Development and Optimization of an Impurity Profiling Method for GLP-1a
- Waters ACQUITY 125A SEC Denaturing SEC-MS Analysis of High Molecular Weight Impurities in GLP-1a
- Waters RPLC/HILIC Impurity Profiling of GLP-1a Using LC-UV/MS
- Waters ACQUITY Premier CSH C18 Ion Mobility Separation of GLP-1a Impurities
- Waters ACQUITY Premier Peptide CSH C18 Temperature Dependence on RP Separations of Fatty Acid Modified GLP-1a and their Impurities
- Waters ACQUITY Premier Peptide HSS T3 Microflow Columns Increase Sensitivity and Reduce Solvent Consumption in GLP-1 Bioanalytical Assay
- Waters ACQUITY UPLC Peptide CSH C18 Improved GLP-1a Peptide Recovery
- Waters Analysis and Characterization of GLP-1a
- Waters BioResolve Peptide Phenyl-Hexyl+ C18+ Separation of a GLP-1a and Structurally Similar Impurities
- Waters BioResolve Peptide Phenyl-Hexyl+ RPLC-MS Analysis of Low-Abundance Impurities in a GLP-1a Therapeutic
- Waters BioResolve Peptide Phenyl-Hexyl+ Robust, Reproducible Separations for Modern Peptide Therapeutics
- Waters Characterizing Quality Attributes of GLP-1a by Light Scattering
- Waters Column Selection for RPLC-UV Impurity Analysis of Fatty Acid Modified GLP-1a
- Waters Method Fevelopment for Forced Degradation of Small Molecule GLP-1a Orforglipron
- Waters Quantification of GLP-1 Receptor Agonists
- Waters XBridge Premier Protein SEC Identification of GLP-1 Analog Oligomeric States using SEC-MALS
- Waters XSelect Premier Peptide CSH C18 GLP-1a: Accelerating Method Development and Manufacturing with LC-UV/MS
- Waters XSelect Premier Peptide CSH C18 Separation Methods for GLP-1 Synthetic Peptides
- Waters XSelect Premier Peptide CSH C18 LC-UV/MS Workflows to Increase Efficiency in Impurity Profiling og GLP-1a
- Waters XSelect Premier Peptide CSH C18 Accelerating Method Development and Manufacturing of GLP-1a with LC-UV/MS
- Waters ACQUITY Premier Peptide CSH C18 Characterization and Impurity Profiling of Combined Amylin and GLP-1a
- Waters XBridge Premier Protein SEC Liraglutide Native SEC-MALS Characterization
- Waters Faster, More Efficient Biotherapeutic Peptide Size-Based Separations
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