Pralatrexate is a folate analogue and antineoplastic active pharmaceutical ingredient (API) used in oncology. It is a structurally modified antifolate that acts primarily through inhibition of dihydrofolate reductase (DHFR) and interference with folate-dependent cellular processes. Pralatrexate is chemically identified by the molecular formula C23H23N7O5, with a molecular weight of 477.48 g/mol and CAS Number 146464-95-1. FDA and PubChem records identify Pralatrexate as a 1:1 racemic mixture of S- and R-diastereomers at the C10 position.
Pralatrexate is an important oncology API used in the manufacture of pharmaceutical products for relapsed or refractory peripheral T-cell lymphoma (PTCL). The FDA-approved product FOLOTYN contains pralatrexate and is administered intravenously. Pralatrexate is classified as an antineoplastic folate analogue and works by competitively inhibiting dihydrofolate reductase as well as folylpolyglutamyl synthetase, resulting in depletion of thymidine and other metabolites required for cellular proliferation.
Pralatrexate is a pteridine-based antifolate structurally related to folate compounds. Its chemical structure contains a pteridine ring, benzoyl linkage, terminal alkyne functionality and an L-glutamic acid-derived portion. The FDA-approved description gives the chemical name as (2S)-2-[[4-[(1RS)-1-[(2,4-diaminopteridin-6-yl)methyl]but-3-ynyl]benzoyl]amino]pentanedioic acid.
A significant characteristic of Pralatrexate is its stereochemistry. Unlike a simple single-stereoisomer API, the approved substance is described as a 1:1 racemic mixture of S- and R-diastereomers at the C10 position. Therefore, stereochemical composition is an important consideration in the characterization and quality control of the API.
Pralatrexate is described as an off-white to yellow solid. More recent drug-substance information describes it as an off-white to yellow hygroscopic powder. It is soluble in dimethyl sulfoxide and has limited solubility in some organic solvents. FDA labeling also reports pKa values around 3.25, 4.70 and 6.0–6.17 depending on the referenced formulation record.
Pralatrexate API is primarily associated with oncology pharmaceutical applications, including:
FOLOTYN is approved for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma. The approved dosage form is an intravenous injection.
Pralatrexate requires careful pharmaceutical quality control because of its complex antifolate structure and defined stereochemical composition. Appropriate API characterization may include identity testing, chromatographic purity, assay, related substances, residual solvents, water content, inorganic residue and stereochemical characterization according to the applicable registered specification.
It is important to distinguish the API specification from the specifications of the finished injection. FDA labeling confirms that the finished injection is supplied at 20 mg/mL, with a formulation pH of 7.5–8.5 and an isotonicity range of 280–300 mOsm. These are finished-product parameters and should not be presented as universal Pralatrexate API release specifications.
Because a complete authoritative public pharmacopoeial API release monograph with numerical limits was not located during this research, unsupported values such as 98–102% assay or arbitrary impurity limits should not be presented as official Pralatrexate API specifications.
A Pralatrexate API manufacturer in India should maintain controlled manufacturing and analytical processes appropriate for an oncology active pharmaceutical ingredient. Particular attention should be given to stereochemical composition, chemical purity, related substances, residual solvents and physical characteristics.
The manufacturing process should also incorporate appropriate controls for hazardous pharmaceutical materials. Pralatrexate-containing products are classified as hazardous drugs, and appropriate handling, containment and occupational-safety procedures are therefore important during manufacturing and processing.
A robust quality system should include validated analytical methods, qualified reference standards, batch traceability and appropriate documentation. Analytical testing should be performed against the applicable customer, regulatory or registered API specification rather than relying on generic small-molecule assumptions.
Pralatrexate API should be packaged in suitable pharmaceutical-grade containers that protect the material from moisture, contamination and environmental exposure. Because recent product information describes the drug substance as hygroscopic, moisture protection is particularly relevant.
For the finished FOLOTYN product, FDA/DailyMed specifies storage at 2–8°C in the original carton to protect from light. This finished-product storage condition should not automatically be transferred to bulk API without supporting API stability data.
Documentation for Pralatrexate API can include:
Pralatrexate is a specialized oncology API with an established pharmaceutical application in relapsed or refractory peripheral T-cell lymphoma. Its defined molecular identity, CAS Number 146464-95-1, 477.48 g/mol molecular weight and characteristic 1:1 S/R diastereomeric composition make accurate API characterization particularly important.
For pharmaceutical companies seeking Pralatrexate API from India, important quality considerations include identity, assay, related substances, stereochemical composition, water content, residual solvents, physical characteristics and complete batch documentation.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |