Ziconotide is a synthetic peptide active pharmaceutical ingredient belonging to the class of N-type calcium channel blockers. It is a synthetic equivalent of omega-conotoxin MVIIA, a peptide originally identified from the venom of the marine cone snail Conus magus. Ziconotide is used as an analgesic for the management of severe chronic pain in appropriately selected patients.
Ziconotide is a highly specialized peptide API. Unlike conventional chemically synthesized small-molecule APIs, its quality depends on peptide sequence, stereochemical integrity, disulfide-bond formation, peptide purity, molecular mass, biological binding activity and control of peptide-related impurities.
Ziconotide has the molecular formula C102H172N36O32S7 and a molecular weight of approximately 2639.2 g/mol. Its CAS Number is 107452-89-1, and its FDA UNII is 7I64C51O16.
The peptide consists of 25 amino acids and contains three disulfide bridges formed between cysteine residues. Its amino-acid sequence is:
Cys-Lys-Gly-Lys-Gly-Ala-Lys-Cys-Ser-Arg-Leu-Met-Tyr-Asp-Cys-Cys-Thr-Gly-Ser-Cys-Arg-Ser-Gly-Lys-Cys-amide
FDA describes Ziconotide as a 25-amino-acid polybasic peptide with three disulfide bridges.
The three-dimensional structure and disulfide-bond arrangement are essential to Ziconotide's biological activity. The peptide contains multiple cysteine residues whose correct pairing produces the characteristic cyclic peptide structure.
EMA describes Ziconotide as a single optical isomer with 21 chiral carbon atoms. The active substance is synthesized from protected amino acids having known L-configurations, with manufacturing controls designed to preserve stereochemistry during synthesis.
Ziconotide produces its analgesic effect by selectively blocking N-type voltage-sensitive calcium channels located on neurons.
N-type calcium channels contribute to the release of neurotransmitters involved in pain transmission. By inhibiting these channels, Ziconotide reduces neurotransmitter release from presynaptic nerve terminals and decreases transmission of nociceptive signals.
Because of this mechanism, Ziconotide represents a pharmacological approach that is fundamentally different from opioid analgesics.
Ziconotide is manufactured using solid-phase peptide synthesis (SPPS). EMA describes the manufacturing process as involving synthesis from protected amino acids, cleavage from the resin, conversion to the acetate form and purification.
Peptide manufacturing requires strict control of amino-acid coupling, protecting groups, deprotection, cleavage, oxidation and disulfide-bond formation. Purification is particularly important because peptide synthesis can generate deletion sequences, truncated peptides, oxidation products and other structurally related substances.
The final API is therefore subjected to multiple orthogonal analytical tests to confirm identity, peptide purity, molecular mass, stereochemical integrity and biological activity.
The pharmaceutical product uses the soluble acetate form of Ziconotide. EMA's scientific assessment specifically identifies ziconotide acetate as the active-substance form supplied for the medicinal product.
The acetate counterion and water content are important quality attributes because the peptide is highly hygroscopic and sensitive to environmental conditions.
Ziconotide requires specialized peptide quality control. EMA reports that the active-substance specification includes appearance, identification, specific rotation, solubility, amino-acid analysis, molecular weight, peptide purity, related substances, residual solvents, heavy metals, endotoxins, peptide content, acetate, water, mass balance and binding assay.
This means that conventional fields such as melting point, residue on ignition and ordinary small-molecule HPLC assay do not adequately describe the quality of Ziconotide API.
Peptide purity is a critical quality attribute for Ziconotide. HPLC-based methods can separate the desired peptide from truncated sequences, deletion peptides, oxidation products and other related substances.
Because Ziconotide is intended for intrathecal administration, control of impurities and endotoxins is particularly important. EMA specifically identifies peptide purity, related substances and bacterial endotoxin testing among the active-substance controls.
Molecular-weight determination is an important identity test for Ziconotide because the expected molecular mass provides confirmation of the synthesized peptide structure.
FDA reports the molecular weight of Ziconotide as approximately 2639 daltons. Mass spectrometry is therefore an appropriate analytical technique for confirming molecular identity and detecting mass-related structural differences.
Ziconotide's biological activity depends on its ability to interact with N-type calcium channels. Consequently, a binding or functional biological assay is an important component of quality evaluation.
EMA identifies a binding assay as part of the active-substance specification.
For a peptide API such as Ziconotide, chemical purity alone does not completely establish biological quality; correct sequence, folding and disulfide connectivity are also important.
Ziconotide is highly sensitive to environmental conditions. EMA describes the active substance as highly hygroscopic, anhydrous, pH-sensitive, heat-sensitive and moisture-sensitive, with susceptibility to oxidative degradation.
The EMA assessment reports storage of the drug substance at −20°C in the presence of desiccant, with manufacturing manipulations performed under a nitrogen atmosphere to minimize oxidative degradation. Stability studies included long-term storage at −20°C and accelerated conditions.
Ziconotide is supplied in a soluble acetate form suitable for pharmaceutical formulation. Solubility is an important identity and quality attribute and is included within the EMA active-substance specification.
For API handling, the peptide should be protected from excessive moisture, heat and oxidative conditions because these factors can influence peptide integrity.
Ziconotide is associated with the treatment of severe chronic pain requiring intrathecal therapy. FDA identifies its pharmacological class as an N-type calcium channel blocker and its route of administration as intrathecal.
The marketed medicinal product contains Ziconotide as a sterile, preservative-free solution intended for continuous intrathecal infusion.
Ziconotide is a specialized peptide API requiring controlled peptide synthesis, purification, structural characterization and biological quality testing.
Swapnroop Drugs & Pharmaceuticals operates as an Indian pharmaceutical raw-material and API supplier with a portfolio covering APIs, excipients and other pharmaceutical materials for domestic and international markets. Its current website emphasizes bulk API supply, DMF-grade quality, pharmaceutical raw materials and global export support.
For Ziconotide, pharmaceutical customers should evaluate peptide identity, purity, molecular mass, related substances, endotoxin, residual solvents, water content and biological activity alongside the applicable regulatory documentation.
Ziconotide is a highly specialized synthetic peptide API consisting of 25 amino acids and three disulfide bridges. It has the molecular formula C102H172N36O32S7, molecular weight approximately 2639.2 g/mol, and CAS Number 107452-89-1.
Its pharmaceutical quality is controlled through peptide-specific analytical and biological methods, including molecular-weight determination, peptide purity, related substances, amino-acid analysis, acetate content, water, endotoxins and binding activity.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Heavy Metals | NMT 20 ppm |
| pH (1% Solution) | 4.0–10.0 |
| Individual Impurity | NMT 0.10% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 5.0% |