Pramlintide API is a synthetic analogue of human amylin, a 37-amino-acid peptide hormone involved in postprandial glucose regulation. Pramlintide differs from human amylin by substitution of proline at positions 25, 28 and 29. The peptide contains a disulfide bond between its two cysteine residues and has a C-terminal tyrosinamide structure.
Pramlintide is supplied pharmaceutically as pramlintide acetate, an acetate salt of the synthetic peptide. FDA describes pramlintide acetate as a white powder that is soluble in water. The marketed drug substance/formulation contains pramlintide as the acetate salt.
Pramlintide is an amylin analogue peptide API developed for use as an adjunct to insulin therapy in diabetes. It is structurally different from conventional small-molecule active pharmaceutical ingredients and therefore requires peptide-specific analytical controls such as reversed-phase HPLC, LC-MS, peptide purity testing and appropriate assessment of related/degradation products.
| Parameter | Value |
|---|---|
| Product Name | Pramlintide |
| Pharmaceutical Form | Pramlintide Acetate |
| CAS Number – Pramlintide | 151126-32-8 |
| CAS Number – Pramlintide Acetate | 196078-30-5 |
| FDA UNII – Pramlintide | D3FM8FA78T |
| FDA UNII – Pramlintide Acetate | 726I6TE06G |
| Peptide Length | 37 amino acids |
| Molecular Formula – Pramlintide | C171H263N51O53S2 estimated by FDA |
| Average Molecular Weight – Pramlintide | ~3950 Da |
| Pramlintide Acetate | Acetate salt / hydrate form |
| Physical Form | White to off-white powder |
| Class | Synthetic amylin analogue / peptide |
| Sequence | KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTY-NH₂ |
FDA's current GSRS record classifies pramlintide as a protein, gives the complete 37-residue sequence and an estimated molecular formula of C171H263N51O53S2 with a calculated sequence molecular weight of approximately 3950 Da.
FDA's drug labeling describes pramlintide acetate as having a molecular formula represented as C171H267N51O53S2·xC2H4O2, with 3 ≤ x ≤ 8, and molecular weight 3949.4 for the labeled material. This reflects the variable acetate/hydration state of the salt and is why a single simple small-molecule formula should not be applied to this peptide.
Pramlintide is a synthetic analogue of human amylin with substitutions at amino acid positions 25, 28 and 29. These substitutions reduce the tendency of the peptide to aggregate while maintaining amylin-like pharmacological activity. The molecule contains two cysteine residues forming an intramolecular disulfide bridge.
Pramlintide is supplied as an acetate salt. FDA identifies pramlintide acetate as a white powder soluble in water.
Because it is a peptide, melting point, residue on ignition and conventional small-molecule physicochemical specifications are not the most appropriate primary quality attributes. Peptide identity, chromatographic purity, molecular mass, related peptides, water/acetate content and microbiological quality are more relevant.
Pramlintide is an amylin analogue used as an adjunct to mealtime insulin therapy in patients with diabetes. It helps reproduce important physiological effects of endogenous amylin, including slowing gastric emptying, increasing satiety and suppressing inappropriate postprandial glucagon secretion.
Pramlintide acetate was approved in the United States in 2005 for use in adults with type 1 or type 2 diabetes who use mealtime insulin and require additional glycemic control.
Pramlintide requires peptide-specific analytical testing rather than relying exclusively on conventional API tests.
Validated RP-HPLC and SCX-HPLC methods have been reported for separating pramlintide from degradation products. LC-MS has also been used to identify degradation products generated under hydrolytic, oxidative and thermal stress conditions.
Important quality attributes can include:
A commercial pharmaceutical-grade certificate publicly available for pramlintide acetate reports HPLC purity ≥99.0%, water content NMT 5.0%, loss on drying NMT 1.0%, individual heavy-metal limits of NMT 0.5 ppm for Pb, As, Hg and Cd, and single impurity <0.8%. These are an enterprise/commercial specification, not a universal USP/IP/BP/Ph Eur monograph limit.
A separate commercial peptide specification reports 98.0% minimum HPLC purity, single impurity NMT 1.0%, peptide content ≥80% by %N, and assay 95.0–105.0% on an anhydrous, acetic-acid-free basis. This demonstrates why the analytical basis must be stated when comparing peptide specifications.
Pramlintide API manufacturing requires peptide synthesis, controlled disulfide-bond formation, purification and final salt/formulation control. Reverse-phase preparative HPLC is commonly used during purification of pramlintide acetate.
Published preparation work has reported final pramlintide acetate purity above 99% by HPLC, demonstrating the feasibility of obtaining highly purified material through controlled peptide synthesis and chromatographic purification.
For pharmaceutical-grade material, manufacturing controls should address peptide sequence identity, purity, related peptides, molecular mass, acetate content, water, residual solvents and microbiological quality.
Pramlintide acetate is a peptide and should be protected from moisture, excessive heat and conditions that could promote degradation.
Commercial peptide material is commonly supplied as a powder in suitable peptide-compatible containers. One commercial pharmaceutical-grade specification recommends storage in a sealed, dark and dry environment below −20°C.
For API manufacture, the actual storage condition should be established through validated stability studies for the specific formulation, salt/hydration state and packaging configuration.
Pramlintide API documentation may include:
Pramlintide is a well-characterized synthetic peptide analogue of human amylin with an established pharmaceutical application in diabetes management. Its 37-amino-acid structure, defined peptide sequence, disulfide bond and acetate salt form require specialized analytical and manufacturing controls.
For pharmaceutical and research applications, high-quality Pramlintide API should be supported by peptide-specific identity, purity, molecular-mass, impurity and stability data rather than generic small-molecule API specifications.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Individual Impurity | NMT 0.8% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 5.0% |
| Melting Point | 150–160°C |