Ipamorelin: Research Profile and Purity Standards

Ipamorelin: Research Profile and Purity Standards

Ipamorelin is a pentapeptide with the amino acid sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2. It is a growth hormone secretagogue (GHS), meaning it stimulates the release of growth hormone (GH) from the pituitary gland. Ipamorelin is often favored in research settings for its selective GH-releasing action, minimizing the release of other hormones like cortisol, which can be a concern with some other GHSs. This article provides a detailed research profile of Ipamorelin, focusing on its molecular structure, mechanism of action, research applications, quality markers, common impurities, and appropriate storage conditions. It aims to equip researchers with the knowledge necessary to critically evaluate Ipamorelin products and ensure the integrity of their research.

Molecular Structure and Properties

Ipamorelin, also known as NNC 26-0161, has the following characteristics:

• Sequence: Aib-His-D-2-Nal-D-Phe-Lys-NH2
• Molecular Formula: C₃₈H₄₉N₉O₅
• Molecular Weight: 711.85 g/mol (anhydrous base)
• CAS Registry Number: 170851-70-4
• Structure Description:
  • Aib: ?-aminoisobutyric acid (a non-proteinogenic amino acid)
  • His: Histidine
  • D-2-Nal: D-2-Naphthylalanine (a non-natural amino acid)
  • D-Phe: D-Phenylalanine
  • Lys: Lysine

The presence of non-natural amino acids like Aib and D-2-Nal contributes to Ipamorelin's resistance to enzymatic degradation, potentially increasing its bioavailability and duration of action. The C-terminal amidation (-NH2) also stabilizes the peptide and is crucial for its activity.

Mechanism of Action

Ipamorelin selectively binds to the growth hormone secretagogue receptor type 1 (GHS-R1a), also known as the ghrelin receptor, located primarily in the pituitary gland and hypothalamus. Activation of GHS-R1a stimulates the release of GH from somatotroph cells in the anterior pituitary. Unlike some other GHSs like GHRP-6, Ipamorelin exhibits high selectivity for GH release, with minimal or no effect on cortisol or prolactin levels at typical research concentrations. This selectivity is thought to be due to differences in the intracellular signaling pathways activated by different GHSs.

Practical Tip: Consider the potential for receptor desensitization with prolonged Ipamorelin administration. Cyclical dosing strategies (e.g., using Ipamorelin for a few weeks followed by a break) may help to maintain receptor sensitivity.

Research Applications

Ipamorelin has been investigated in various research areas, including:

• Growth Hormone Deficiency: Studying the potential of GHSs to stimulate endogenous GH production in individuals with GH deficiency.
• Muscle Growth and Repair: Investigating the effects of increased GH levels on muscle protein synthesis, muscle mass, and recovery from injury.
• Bone Density: Exploring the role of GH in bone remodeling and the potential of Ipamorelin to improve bone density.
• Metabolic Regulation: Examining the impact of GH on glucose metabolism, lipid metabolism, and insulin sensitivity.
• Aging Research: Investigating the effects of GH on various age-related physiological processes.

Important Note: Ipamorelin is intended for research purposes only and is not approved for human use as a therapeutic agent.

Quality Markers and Assessment

Ensuring the quality of Ipamorelin is critical for obtaining reliable and reproducible research results. Key quality markers include purity, peptide content, amino acid analysis, water content, counterion content, and presence of impurities.

Purity

Purity refers to the percentage of the desired peptide sequence in the product. It is typically determined by High-Performance Liquid Chromatography (HPLC) and reported as a percentage. A minimum purity of 98% is generally recommended for research purposes. Higher purity levels (e.g., >99%) may be required for more sensitive applications.

HPLC Analysis: HPLC separates peptides based on their physicochemical properties (e.g., hydrophobicity). The area under the peak corresponding to Ipamorelin is divided by the total area of all peaks to determine the purity. The HPLC method should be validated to ensure its accuracy and reliability.

Practical Tip: Request a representative HPLC chromatogram from the supplier to visually assess the purity and identify any major impurities.

Peptide Content

Peptide content reflects the actual amount of Ipamorelin in the product, accounting for factors such as water content, counterion content, and residual solvents. It is typically expressed as a percentage or as mg/vial. A peptide content closer to the theoretical value (based on the molecular weight) indicates a higher quality product.

Example: A vial labeled as containing 5 mg of Ipamorelin may have a peptide content of only 4.5 mg due to the presence of water and counterions. This means that you are actually receiving 90% of the stated amount of Ipamorelin.

Amino Acid Analysis (AAA)

AAA is a quantitative method used to determine the amino acid composition of the peptide. It confirms the presence of the correct amino acids in the expected ratios. Deviations from the theoretical ratios can indicate peptide degradation, incomplete synthesis, or the presence of incorrect amino acids.

Practical Tip: AAA is a valuable tool for verifying the identity and integrity of the peptide, especially for larger or more complex peptides. However, it's not always routinely performed for smaller peptides like Ipamorelin due to cost considerations. Requesting AAA data can provide added assurance of quality.

Water Content

Peptides are hygroscopic and can absorb water from the environment. Excessive water content can affect the peptide content and stability. Water content is typically determined by Karl Fischer titration and should ideally be below 5%. Higher water content can contribute to peptide degradation over time.

Counterion Content

During peptide synthesis, counterions (e.g., acetate, trifluoroacetate (TFA)) are often used to neutralize the charge of the peptide. The presence of counterions can affect the peptide content and stability. Trifluoroacetate (TFA) is a common counterion used in peptide synthesis. While TFA is generally considered safe at low levels, it can potentially interfere with some biological assays and may be undesirable in certain applications. Suppliers should provide information on the counterion used and its content.

Practical Tip: Inquire about the counterion used during synthesis. If TFA is a concern, consider requesting a peptide synthesized with an alternative counterion, such as acetate.

Appearance

Ipamorelin typically appears as a white to off-white lyophilized powder. Any discoloration or clumping may indicate degradation or contamination.

Common Impurities

Peptide synthesis is not a perfect process, and various impurities can be present in the final product. Common impurities include:

• Truncated Sequences: Peptides with one or more amino acids missing from the sequence.
• Deletion Sequences: Peptides with one or more amino acids deleted from within the sequence.
• Modified Amino Acids: Amino acids that have been chemically modified during synthesis (e.g., oxidation of methionine).
• Diastereomers: Isomers resulting from incomplete racemization during synthesis of D-amino acids.
• Solvents and Reagents: Residual solvents (e.g., acetonitrile, DMF) and reagents used during synthesis.

The presence of these impurities can affect the biological activity of the peptide and potentially lead to inaccurate research results. High-quality suppliers employ purification techniques (e.g., HPLC) to minimize the levels of these impurities.

Practical Tip: Request information on the purification methods used by the supplier to remove impurities. Multi-step purification processes are generally more effective than single-step methods.

Storage Requirements

Proper storage is essential to maintain the stability and integrity of Ipamorelin. The following storage guidelines are recommended:

• Lyophilized Powder: Store at -20°C or below. Protect from light and moisture. Under these conditions, Ipamorelin is generally stable for at least 2 years.
• Reconstituted Solution: Reconstitute with sterile water or a suitable buffer. Store at 2-8°C (refrigerated) for short-term storage (days to weeks). For longer-term storage of solutions, consider aliquoting and freezing at -20°C or below. Avoid repeated freeze-thaw cycles.

Practical Tip: Always record the date of reconstitution on the vial. Discard any reconstituted solution that shows signs of degradation (e.g., discoloration, cloudiness). Use within the recommended timeframe.

Note: The stability of Ipamorelin solutions can vary depending on the solvent, concentration, and storage conditions. It is always best practice to prepare fresh solutions whenever possible.

Sourcing Considerations

Choosing a reputable supplier is crucial for obtaining high-quality Ipamorelin. Consider the following factors when selecting a supplier:

• Certificate of Analysis (CoA): The supplier should provide a CoA that includes information on purity, peptide content, amino acid analysis (if available), water content, counterion content, and any other relevant quality control data.
• Manufacturing Standards: Look for suppliers that adhere to Good Manufacturing Practices (GMP) or similar quality standards.
• Reputation and Reviews: Check the supplier's reputation and read reviews from other researchers.
• Customer Support: Ensure the supplier provides responsive and helpful customer support.
• Price: While price is a factor, prioritize quality over cost. A lower price may indicate a lower-quality product.

Practical Tip: Request a sample of the Ipamorelin from the supplier and test it independently to verify its quality before placing a large order. Consider sending the sample to a third-party analytical laboratory for independent testing.

Key Takeaways

• Ipamorelin is a selective growth hormone secretagogue with potential applications in various research areas.
• Purity, peptide content, amino acid analysis, water content, and counterion content are key quality markers to assess.
• HPLC is the primary method for determining peptide purity.
• Common impurities include truncated sequences, deletion sequences, and modified amino acids.
• Proper storage at -20°C or below is essential for maintaining the stability of the lyophilized powder.
• Choose a reputable supplier that provides a Certificate of Analysis and adheres to high manufacturing standards.
• Consider independent testing to verify the quality of the Ipamorelin.