Melphalan Flufenamide API Manufacturer in India

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Melphalan Flufenamide API

Melphalan Flufenamide, also known as melflufen, is a peptide-conjugated alkylating agent and prodrug of melphalan. It is designed to enter cells efficiently and undergo enzymatic cleavage by aminopeptidases to release the active alkylating agent melphalan.

Melphalan Flufenamide is a specialized oncology pharmaceutical compound associated with multiple myeloma research and treatment. Its mechanism involves release of melphalan, which alkylates DNA and produces DNA cross-linking, thereby inhibiting DNA and RNA synthesis and promoting tumor-cell death.

Melphalan Flufenamide API Manufacturer in India

Melphalan Flufenamide is a specialized oncology pharmaceutical API / drug substance requiring stringent control of identity, purity, related substances, stereochemical integrity and residual solvents.

Chemical Information

CAS Number: 380449-51-4
Molecular Formula: C24H30Cl2FN3O3
Molecular Weight: 498.42 g/mol
Synonyms: Melflufen, Prodrug J-1, J-1
Development Name: J-1
Drug Class: Alkylating Agent
Therapeutic Class: Antineoplastic Agent
Therapeutic Area: Oncology / Hematology
Molecule Type: Peptide-Conjugated Small-Molecule Prodrug

The free-base form has a molecular weight of approximately 498.4 g/mol. The hydrochloride salt has molecular formula C24H31Cl3FN3O3 and molecular weight 534.9 g/mol.

Mechanism of Action

Melphalan Flufenamide is a prodrug of melphalan. Its lipophilic structure facilitates cellular uptake, after which aminopeptidases can cleave the compound to release melphalan.

Released melphalan acts as an alkylating agent and:

  • Alkylates DNA
  • Produces DNA interstrand and intrastrand cross-links
  • Inhibits DNA and RNA synthesis
  • Promotes apoptosis
  • Inhibits proliferation of susceptible tumor cells

 

Pharmaceutical Applications

Melphalan Flufenamide is associated with pharmaceutical applications involving:

  • Multiple myeloma
  • Relapsed or refractory multiple myeloma
  • Antineoplastic drug development
  • Alkylating-agent research
  • Oncology pharmaceutical research
  • Aminopeptidase-targeted drug delivery

Dosage Form Applications

Melphalan Flufenamide hydrochloride has been developed as a sterile lyophilized powder for intravenous administration. The FDA description identifies the product as a single-dose vial containing melphalan flufenamide equivalent to the hydrochloride salt.

Physical and Chemical Characteristics

Melphalan Flufenamide is a relatively lipophilic prodrug designed for cellular uptake. The hydrochloride form is sparsely soluble in aqueous solutions and soluble in most organic solvents, with a reported pKa of 7.13.

Manufacturing Process

A controlled Melphalan Flufenamide API manufacturing process may involve:

  1. Qualification of starting materials
  2. Preparation of protected amino-acid intermediates
  3. Controlled peptide coupling
  4. Assembly of the required peptide-drug structure
  5. Deprotection
  6. Hydrochloride salt formation, where applicable
  7. Purification
  8. Crystallization or isolation
  9. Controlled drying
  10. Final analytical characterization
  11. Pharmaceutical-grade packaging

Quality Control Testing

Typical Melphalan Flufenamide API testing may include:

  • Identification by IR
  • HPLC identification
  • LC-MS characterization
  • Assay
  • Related substances
  • Degradation products
  • Stereochemical purity
  • Residual solvents
  • Water content
  • Elemental impurities
  • Specific optical rotation
  • Stability testing

Storage

Store Melphalan Flufenamide under validated pharmaceutical storage conditions, protected from excessive moisture, heat and direct light. Exact storage requirements should follow the applicable approved specification and stability data.

Pharmaceutical Research

Melphalan Flufenamide is relevant to research involving:

  • Multiple myeloma
  • Alkylating agents
  • Melphalan
  • Aminopeptidases
  • DNA alkylation
  • DNA cross-linking
  • Antineoplastic drug development
  • Targeted intracellular drug release

Regulatory Note

The distinction between Melphalan Flufenamide free base (CAS 380449-51-4) and Melphalan Flufenamide Hydrochloride (CAS 380449-54-7) is important for CMS data. The FDA labeling describes the hydrochloride salt as the drug substance used in the product.

Detailed 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%
Residue on Ignition NMT 0.5%
Heavy Metals NMT 10 ppm
Total Impurities NMT 1.0%
Water Content NMT 1.0%
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