Methotrexate API

Methotrexate API refers to the Active Pharmaceutical Ingredient form of methotrexate — the pure chemical substance used to manufacture methotrexate-containing medicines.

Here’s a detailed overview:

1. Basic Information

Name: Methotrexate

Chemical Name: (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid

Molecular Formula: C₂₀H₂₂N₈O₅

Molecular Weight: 454.44 g/mol

CAS Number: 59-05-2

Appearance: Yellow to orange crystalline powder

Solubility: Slightly soluble in water; insoluble in most organic solvents

Stability: Sensitive to light; should be stored in airtight containers, away from light and moisture

2. Pharmacological Class

Class: Antimetabolite, Antifolate

Type: Cytotoxic / Chemotherapy agent and immunosuppressant

WHO Essential Medicines List: Included

3. Mechanism of Action

Methotrexate inhibits dihydrofolate reductase (DHFR) — an enzyme needed for DNA synthesis and cell replication.

This blocks the conversion of dihydrofolate to tetrahydrofolate.

As a result, synthesis of purines and thymidylate (DNA building blocks) is disrupted.

Rapidly dividing cells (e.g., cancer cells, activated immune cells) are most affected.

4. Medical Uses

Methotrexate API is formulated into tablets, injections, or infusions for:

Cancer treatment: Acute lymphoblastic leukemia, lymphoma, breast cancer, osteosarcoma, head & neck cancers, etc.

Autoimmune diseases (low dose): Rheumatoid arthritis, psoriasis, Crohn’s disease

Ectopic pregnancy: Non-surgical termination in selected cases

5. Dosage Form Examples

From API, manufacturers produce:

Oral tablets (2.5 mg, 5 mg, 10 mg, etc.)

Injectables (solution for injection, lyophilized powder for reconstitution)

6. Manufacturing Notes

API production requires strict GMP compliance due to its cytotoxicity.

Operators must use special containment systems to prevent exposure.

Methotrexate is hazardous—waste disposal and handling must meet environmental and occupational safety standards.

7. Safety Profile

Common side effects: Nausea, fatigue, mouth ulcers, hair loss

Serious risks: Bone marrow suppression, hepatotoxicity, pulmonary fibrosis, teratogenicity

Requires regular monitoring of blood counts, liver and kidney function in patients.