Roxadustat is a synthetic small-molecule active pharmaceutical ingredient belonging to the class of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). It is used in pharmaceutical products for the treatment of symptomatic anaemia associated with chronic kidney disease (CKD). Roxadustat has become an important API in the development and manufacture of oral medicines designed to stimulate the body's physiological response to reduced oxygen availability. The European Medicines Agency identifies roxadustat as the active substance in Evrenzo and classifies it under ATC code B03XA05.
Roxadustat is also known by development names including FG-4592, FG4592 and ASP1517. Its chemical formula is C₁₉H₁₆N₂O₅, with a molecular weight of 352.34 g/mol. The principal CAS Number is 808118-40-3. PubChem identifies Roxadustat as an N-acylglycine and HIF-PH inhibitor.
Roxadustat is generally supplied as a powder or crystalline solid. Commercial analytical references describe it as white to beige or off-white in appearance. Its physicochemical properties should be controlled according to the validated specification applicable to the intended pharmaceutical grade.
Roxadustat acts by inhibiting hypoxia-inducible factor prolyl hydroxylase enzymes. Under normal oxygen conditions, these enzymes contribute to the degradation of HIF proteins. Inhibition of HIF-PH promotes stabilization of HIF signalling and increases the transcriptional response associated with erythropoiesis and iron metabolism.
This mechanism is particularly relevant in chronic kidney disease, where impaired kidney function can reduce endogenous erythropoietin production and contribute to anaemia. The EMA states that roxadustat stimulates the natural response that normally occurs under low-oxygen conditions, including increased production of erythropoietin and haemoglobin.
Roxadustat API is used in the manufacture of oral pharmaceutical formulations for the treatment of anaemia associated with chronic kidney disease. The authorised European product Evrenzo is available as film-coated tablets containing 20 mg, 50 mg, 70 mg, 100 mg or 150 mg of roxadustat.
The EMA indicates that Evrenzo is intended for adult patients with symptomatic anaemia associated with CKD, including patients who are dialysis-dependent and those who are not on dialysis.
Quality control of Roxadustat API should include comprehensive identity, assay, related-substance, residual-solvent, water-content and other applicable pharmaceutical-quality testing according to the validated product specification.
For identity testing, techniques such as IR, HPLC retention time and LC-MS may be used as appropriate. HPLC or an equivalent validated chromatographic procedure is used for assay and related-substance evaluation.
Because there is no universal current USP/Ph. Eur. numerical API monograph specification identified for Roxadustat, numerical acceptance limits should be taken from the applicable approved specification, DMF/ASMF, customer specification or validated manufacturer specification rather than being presented as pharmacopoeial requirements.
Roxadustat API is relevant to pharmaceutical manufacturers developing and producing oral solid dosage formulations for CKD-associated anaemia. API quality should be supported through appropriate analytical controls, batch documentation and regulatory-quality documentation.
Typical documentation can include a Certificate of Analysis (CoA), specification sheet, Safety Data Sheet (SDS/MSDS), Certificate of Origin and applicable regulatory documentation, depending on the market and customer requirements.
Roxadustat should be protected from moisture and stored in a tightly closed container under controlled conditions appropriate to the validated API specification. Research-grade commercial references recommend low-temperature storage, while pharmaceutical API storage conditions should ultimately follow the approved product specification and stability data.
Roxadustat is an established HIF-PH inhibitor with regulatory approval for the treatment of symptomatic anaemia associated with CKD in several markets. Its pharmaceutical development requires careful control of identity, assay, related substances, residual solvents and physical properties. Consistent analytical testing and comprehensive documentation are therefore important for reliable Roxadustat API manufacturing and formulation development.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 99–101% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Total Impurities | NMT 0.5% |