Pyrimethamine is a synthetic antiprotozoal and antimalarial API belonging to the aminopyrimidine class. It acts primarily as an inhibitor of dihydrofolate reductase (DHFR) and interferes with folate metabolism in susceptible protozoa.
Pyrimethamine is used principally in combination regimens for the treatment of toxoplasmosis and certain other protozoal infections. It has also historically been used as an antimalarial, although resistance has limited its use as a standalone malaria treatment. PubChem identifies pyrimethamine as an aminopyrimidine, antiprotozoal, antimalarial and DHFR inhibitor.
The molecular identity and numerical physicochemical data are supported by PubChem and NIST.
Pyrimethamine belongs to the aminopyrimidine antiprotozoal class and functions as a dihydrofolate reductase inhibitor.
Pyrimethamine inhibits the enzyme dihydrofolate reductase (DHFR) in susceptible protozoa. Inhibition of DHFR interferes with the conversion of dihydrofolate to tetrahydrofolate, reducing the availability of folate derivatives required for nucleotide synthesis and cellular replication.
This antifolate mechanism contributes to its antiprotozoal activity and is particularly relevant to treatment of Toxoplasma gondii infections.
Pyrimethamine API is used in pharmaceutical formulations and combination therapies for:
Pyrimethamine is commonly used with leucovorin (folinic acid) to reduce toxicity associated with folate antagonism. PubChem identifies its use as an antimalarial and in combination with a sulfonamide for toxoplasmosis.
Pyrimethamine is described as an odorless, white crystalline powder.
NIST confirms a molecular weight of 248.711 g/mol and CAS number 58-14-0.
A reported melting range for pyrimethamine is approximately 233–234°C. Because melting-point values can vary with measurement method and material form, this value should be treated as a reference physical property rather than an API release specification.
| Property | Value |
|---|---|
| Molecular Weight | 248.71 g/mol |
| Exact Mass | 248.0828741 Da |
| XLogP3 | 2.7 |
| H-Bond Donors | 2 |
| H-Bond Acceptors | 4 |
| Rotatable Bonds | 2 |
| TPSA | 77.8 Ų |
| Melting Point | Approx. 233–234°C |
PubChem reports the calculated molecular descriptors, while NIST provides the molecular formula and molecular weight.
Pyrimethamine API can be characterized using:
Chromatographic testing is particularly important for determining assay, degradation products and process-related impurities.
Quality control for Pyrimethamine API should address:
Pyrimethamine is listed in PubChem with references to USP and WHO International Pharmacopoeia monographs, indicating established pharmacopoeial recognition.
Specific numerical acceptance limits should be taken from the applicable current pharmacopoeial monograph or registered API specification rather than using unsupported generic limits.
Pyrimethamine contains no stereogenic center in its standard chemical structure. Therefore, stereochemical/chiral purity is not applicable as a routine API specification.
Pyrimethamine should be stored according to the applicable pharmacopoeial and approved API stability requirements.
Recommended handling practices include:
Typical pharmaceutical API documentation may include:
Pyrimethamine API manufacturing involves controlled synthesis, purification, isolation, drying and analytical testing. Critical quality attributes include chemical identity, assay, related substances, residual solvents and physical characteristics.
The finished API should comply with the applicable current pharmacopoeial or registered specification.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Melting Point | Approx. 233–234°C reference value |