Pexidartinib API is a small-molecule tyrosine kinase inhibitor used in pharmaceutical development for the treatment of symptomatic tenosynovial giant cell tumor (TGCT) in appropriate adult patients. The active pharmaceutical ingredient is associated with inhibition of colony-stimulating factor 1 receptor (CSF1R), KIT, and FLT3, making it an important targeted oncology API.
The pharmaceutical form is Pexidartinib Hydrochloride, the hydrochloride salt of pexidartinib. The FDA Global Substance Registration System identifies Pexidartinib Hydrochloride as the salt/solvate of the pexidartinib active moiety, with UNII YS6WAI3XN7.
Pexidartinib Hydrochloride has the molecular formula C₂₀H₁₅ClF₃N₅·HCl, corresponding to C₂₀H₁₆Cl₂F₃N₅, and a molecular weight of 454.28 g/mol. The CAS number for the hydrochloride salt is 2040295-03-0, while the free-base active moiety has CAS 1029044-16-3 and molecular weight 417.81 g/mol.
Pexidartinib is a targeted kinase inhibitor with activity against CSF1R, KIT, and FLT3. Its inhibition of CSF1R signaling is particularly relevant to TGCT, where CSF1R signaling contributes to abnormal synovial macrophage accumulation. Pexidartinib is marketed as TURALIO in capsule form.
The API is therefore relevant to pharmaceutical manufacturers and formulation developers working with targeted oncology products. Accurate control of the hydrochloride salt form is important because the free base and hydrochloride have different molecular weights and chemical identities.
Pexidartinib Hydrochloride is described in the FDA-approved labeling as an off-white to white solid. The label states that its aqueous solubility decreases as pH increases. It is soluble in methanol, slightly soluble in water and ethanol, and practically insoluble in heptane. The reported pKa values for the conjugate acids are 2.6 and 5.4.
The API is achiral and has no defined stereocenters according to the FDA substance record.
Pexidartinib Hydrochloride API should be evaluated using validated analytical procedures appropriate for the drug substance. Identification, assay, related substances, residual solvents, elemental impurities, water content, and other applicable quality attributes should be controlled according to the approved API specification and applicable ICH/pharmacopoeial requirements.
Because a universal public pharmacopoeial numerical release specification was not verified for several CMS parameters, values such as assay limits, individual impurities, total impurities, water content, residue on ignition, and pH should not be filled with generic pharmaceutical limits unless they are supported by the manufacturer's approved specification.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.2% |
| Heavy Metals | NMT 10 ppm |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |