Methotrexate Sodium

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Cat Number

API0232801

CAS Number

7413-34-5

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Product Detail Description Scientific Support Customer Q&A

CAS Number

7413-34-5

EINECS

231-022-0

Synonyms

Methotrexate disodium salt, Sodium methotrexate

Molecular Formula

C20H20N8Na2O5

Molecular Weight

498.4

Smiles

CN(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)N[C@@H](CCC(=O)[O-])C(=O)[O-].[Na+].[Na+]

General Description

Methotrexate sodium is the sodium salt of methotrexate, an antimetabolite and antifolate agent that inhibits DNA synthesis and cell division. It is also an immunosuppressant and anti-tumor agent, used for rheumatoid arthritis and in the research of various cancers.

Mechanism of Action

Methotrexate competitively inhibits dihydrofolate reductase, preventing conversion of dihydrofolate to tetrahydrofolate and thereby blocking nucleotide synthesis required for DNA and RNA production. In autoimmune diseases, methotrexate polyglutamates inhibit AICAR transformylase, leading to intracellular adenosine accumulation and potent anti-inflammatory effects. It exerts its cytotoxic activity primarily during the S-phase of the cell cycle, affecting rapidly dividing cells in malignancies and inflammatory conditions.

Application

Methotrexate sodium is indicated for acute lymphoblastic leukemia, non-Hodgkin lymphoma, breast cancer, lung cancer, and osteosarcoma as part of combination chemotherapy regimens. It is also approved for management of severe psoriasis, active rheumatoid arthritis, and polyarticular juvenile idiopathic arthritis when conventional therapy fails.

Ramsey LB, et al. summarized that for high-dose methotrexate (HDMTX) infusions lasting ≤24 hours, the panel recommends considering glucarpidase when the 36-hour methotrexate concentration exceeds 30 μM, the 42-hour concentration exceeds 10 μM, or the 48-hour concentration exceeds 5 μM, particularly when accompanied by significantly elevated serum creatinine indicative of acute kidney injury. For infusions lasting 36 to 42 hours, glucarpidase may be indicated when the 48-hour methotrexate concentration exceeds 5 μM. Optimal administration should occur within 48 to 60 hours from infusion initiation to prevent life-threatening toxicities.

Fig. 1 Standard leucovorin nomogram used in the U.S. Glucarpidase use may be indicated when MTX concentrations are within the shaded area. (Ramsey LB, et al., 2018)

References

Ramsey LB, et al. Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance. Oncologist. 2018;23(1):52-61.

Does Methotrexate Sodium require strict protection from light?

Yes, it is highly photosensitive. Degradation upon light exposure is rapid. It must be stored in light-resistant, amber containers and handled under subdued light.

What is the recommended storage temperature for Methotrexate Sodium?

Store at 2-8°C in a refrigerator. It is thermally labile, and higher temperatures can accelerate degradation, leading to loss of potency and increased impurities.

Is Methotrexate Sodium stable in solution for injection?

Reconstituted solutions have limited stability. They should be used promptly and protected from light.

How is the degradation product 4-aminopteroylglutamic acid monitored?

This key degradation product is specifically quantified using a stability-indicating HPLC method, ensuring it remains below the established limit throughout the product's shelf life.