Rucaparib API is a synthetic small-molecule anticancer active pharmaceutical ingredient belonging to the poly(ADP-ribose) polymerase (PARP) inhibitor class. Rucaparib is designed to inhibit PARP enzymes involved in DNA damage repair, making it particularly relevant to the treatment of cancers associated with defects in homologous recombination repair, including tumors carrying deleterious BRCA1 or BRCA2 mutations.
The pharmaceutical substance used in the marketed product is rucaparib camsylate, a 1:1 salt of rucaparib with (1S,4R)-camphorsulfonic acid. FDA GSRS identifies rucaparib camsylate separately from the active rucaparib moiety and assigns it the molecular formula C₁₉H₁₈FN₃O·C₁₀H₁₆O₄S and molecular weight 555.66 g/mol.
Rucaparib itself has the molecular formula C₁₉H₁₈FN₃O, molecular weight 323.36 g/mol, and CAS Number 283173-50-2. FDA identifies rucaparib as the active form in the substance hierarchy.
Rucaparib is a nitrogen-containing heterocyclic compound containing a fluorinated aromatic system and a methylaminomethyl phenyl substituent. The molecule belongs to the azepinoindole chemical family.
For pharmaceutical manufacturing, the camsylate salt form is particularly important because this is the salt form associated with the marketed pharmaceutical substance. The camsylate contains one molecule of rucaparib associated with one molecule of camphorsulfonic acid. FDA GSRS records two defined stereocenters in the camsylate component associated with the camphorsulfonate moiety.
Rucaparib API is used in oncology formulations as a PARP inhibitor.
The current U.S. prescribing information identifies Rubraca (rucaparib) for:
The current FDA-approved tablet strengths are 200 mg, 250 mg and 300 mg, with a recommended dose of 600 mg twice daily for the labeled indications.
Rucaparib inhibits PARP1, PARP2 and PARP3, enzymes involved in detecting and responding to DNA damage.
PARP inhibition interferes with PARP-mediated DNA repair processes and can result in accumulation of DNA damage. In tumor cells with deficiencies in homologous recombination repair, particularly those associated with deleterious BRCA mutations, inhibition of PARP can result in increased genomic instability and cancer-cell death.
This mechanism forms the basis for the use of rucaparib as a targeted oncology treatment.
Rucaparib camsylate requires comprehensive API quality control covering chemical identity, assay, salt composition, related substances and physical characteristics.
The EMA assessment specifically reports that the active-substance specification includes appearance, IR identification, HPLC assay, camphorsulfonic-acid assay by ion chromatography, related substances by HPLC, residual solvents by GC, water by Karl Fischer, particle size according to Ph. Eur., and inorganic impurities by residue on ignition.
The EMA review also reports that impurities above the applicable ICH Q3A qualification threshold were appropriately qualified and that the analytical methods were suitably validated. Stability studies included assay, related substances, water, polymorphic form and microbiological evaluation.
Rucaparib camsylate is produced through controlled chemical synthesis followed by purification and formation of the specified camsylate salt.
A pharmaceutical manufacturing process should control critical raw materials, reaction parameters, process-related impurities, purification, salt formation and solid-state characteristics. Final API testing should confirm identity, potency, purity, residual solvents, water content, inorganic residues and other critical quality attributes.
Because the API is a defined salt, appropriate control of the rucaparib-to-camphorsulfonate stoichiometry is an important part of pharmaceutical substance characterization.
Rucaparib free base has a molecular weight of 323.36 g/mol, while rucaparib camsylate has a molecular weight of approximately 555.66–555.70 g/mol, depending on the reporting precision. FDA GSRS gives 555.66 g/mol, while PubChem reports 555.7 g/mol.
The rucaparib camsylate molecular formula is C₂₉H₃₄FN₃O₅S. PubChem identifies the camsylate as a camphorsulfonate salt and gives CAS 1859053-21-6.
Rucaparib camsylate API should be packed in suitable pharmaceutical-grade containers that protect the material from moisture, contamination and excessive environmental exposure.
The EMA stability assessment reported long-term active-substance stability at 25°C/60% RH for up to 24 months and accelerated stability at 40°C/75% RH for up to 6 months. The assessment also noted slight photosensitivity and indicated that the opaque container-closure system provided adequate protection from light.
Actual commercial API storage should follow the approved manufacturer specification and validated stability program.
A qualified Rucaparib API manufacturer can provide:
A qualified Rucaparib API manufacturer in India can support pharmaceutical companies developing and manufacturing oncology products requiring controlled-quality rucaparib camsylate.
For this API, particular attention should be given to salt identity, assay, camphorsulfonic-acid content, related substances, residual solvents, water, particle size and solid-state characteristics. These quality attributes are specifically reflected in the EMA active-substance control strategy.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |