Fludarabine Phosphate is a fluorinated purine nucleotide analogue and antineoplastic antimetabolite. It is chemically known as 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-β-D-arabinofuranosyl) and is also known as 2-fluoro-ara-AMP.
Fludarabine phosphate has the molecular formula C₁₀H₁₃FN₅O₇P and molecular weight 365.21 g/mol. The CAS Registry Number is 75607-67-9.
Fludarabine phosphate is a nucleotide metabolic inhibitor. After administration, it is rapidly converted to 2-fluoro-ara-A, which enters cells and is subsequently converted intracellularly to the active triphosphate metabolite 2-fluoro-ara-ATP.
The active metabolite interferes with DNA synthesis by inhibiting enzymes involved in DNA replication, including DNA polymerase and ribonucleotide reductase, and can function as a DNA chain terminator after incorporation into DNA.
USP specifies Fludarabine Phosphate at NLT 98.0% and NMT 102.0%, calculated on the anhydrous, solvent-free basis.
Fludarabine phosphate is used as an antineoplastic agent, particularly in the treatment of certain hematological malignancies. It is available in pharmaceutical formulations including injectable products and, historically, oral film-coated tablets.
Fludarabine phosphate is converted to 2-fluoro-ara-A and then intracellularly phosphorylated to 2-fluoro-ara-ATP. The active metabolite competes with deoxyadenosine triphosphate and interferes with DNA synthesis. It inhibits DNA polymerases, ribonucleotide reductase, DNA primase and DNA ligase I, while incorporation into DNA can cause chain termination.
Fludarabine phosphate injection is available as a sterile pharmaceutical preparation. One USP-labeled injectable product contains 50 mg fludarabine phosphate per vial, together with mannitol and sodium hydroxide for pH adjustment. After reconstitution with 2 mL Sterile Water for Injection, the solution contains 25 mg/mL fludarabine phosphate. The final-product pH range is 7.2–8.2 for that formulation.
Another marketed injection presentation contains 25 mg/mL fludarabine phosphate with a final-product pH range of 7.3–7.7.
Therefore, do not use an injection pH value as the API pH specification. The API and finished dosage form have different specifications.
| Parameter | Specification |
|---|---|
| Appearance | White to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | NLT 98.0% by HPLC |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Heavy Metals | NMT 20 ppm |
| pH (1% Solution) | 7.2–8.2 |