Nitisinone is a synthetic 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor used as an active pharmaceutical ingredient in the management of rare inherited metabolic disorders. It is particularly established in the treatment of hereditary tyrosinemia type 1 (HT-1) and is also used for the reduction of urinary homogentisic acid in adults with alkaptonuria (AKU). PubChem identifies Nitisinone as a reversible inhibitor of 4-hydroxyphenylpyruvate dioxygenase.
Nitisinone is also known by the development code NTBC and is chemically classified as a substituted cyclohexane-1,3-dione derivative. It is a specialized pharmaceutical molecule used in metabolic-disease treatment and research.
Nitisinone is a specialized metabolic disorder pharmaceutical API used for pharmaceutical formulation development, analytical research and manufacture of medicines for approved metabolic indications.
Important API quality attributes include:
Nitisinone is a prescription pharmaceutical substance and its quality specifications should be established using the applicable approved API specification and validated analytical methods.
Product Name: Nitisinone
Synonyms: NTBC; Orfadin; 2-(2-Nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione
CAS Number: 104206-65-7
Molecular Formula: C14H10F3NO5
Molecular Weight: 329.23 g/mol
IUPAC Name: 2-[2-nitro-4-(trifluoromethyl)benzoyl]cyclohexane-1,3-dione
Development Code: NTBC
Drug Class: 4-Hydroxyphenylpyruvate Dioxygenase Inhibitor
Therapeutic Class: Metabolic Disorder Agent
Therapeutic Area: Inherited Metabolic Disorders
Molecule Type: Synthetic Small Molecule
PubChem and FDA/NIH substance records confirm the CAS number 104206-65-7, molecular formula C14H10F3NO5, and molecular weight 329.23 g/mol.
Nitisinone is a reversible inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD), an enzyme involved in the catabolism of tyrosine.
Its pharmacological action results in:
FDA pharmacological classification identifies Nitisinone as a 4-Hydroxyphenyl-Pyruvate Dioxygenase Inhibitor.
Nitisinone API is relevant to:
Nitisinone is established in the treatment of hereditary tyrosinemia type 1, a rare inherited disorder affecting tyrosine metabolism.
By inhibiting HPPD, Nitisinone prevents formation of downstream metabolites involved in the disease pathway. It is used together with dietary restriction of tyrosine and phenylalanine according to approved clinical use.
Nitisinone is also used in adults with alkaptonuria, where its HPPD-inhibitory action reduces production of homogentisic acid (HGA).
PubChem identifies Nitisinone under the HPPD inhibitor class and notes its use for reduction of urinary HGA in adults with alkaptonuria.
Nitisinone is a synthetic small-molecule pharmaceutical substance with a cyclohexane-1,3-dione structure substituted by a nitro- and trifluoromethyl-containing benzoyl group.
PubChem reports:
These are chemical descriptor values rather than pharmaceutical release specifications.
Nitisinone has limited aqueous solubility. Solubility can vary depending on pH, solvent system, temperature and solid-state characteristics.
For CMS purposes, a specific numerical solubility value should not be presented as a universal API specification unless it is supported by the applicable validated technical specification.
A controlled Nitisinone API manufacturing process may involve:
The exact commercial synthesis route should be based on the manufacturer's validated process and applicable regulatory documentation.
Typical pharmaceutical-grade Nitisinone testing may include:
Nitisinone is a specialized prescription API, and a current universally applicable pharmacopoeial numerical assay limit could not be reliably verified from the authoritative public sources reviewed.
Therefore, for a commercial CMS page, the assay should be stated as:
Specification-dependent; use current approved API specification.
This avoids incorrectly applying a generic 98–102% pharmaceutical API limit.
Related-substance testing is important for Nitisinone because process-related and degradation impurities must be controlled using validated chromatographic methods.
For a commercial API page, individual and total impurity limits should be taken from the manufacturer's approved specification or applicable regulatory dossier rather than using generic numerical limits.
Elemental impurities should be controlled according to applicable pharmaceutical requirements, including ICH Q3D principles where applicable.
A generic heavy-metal numerical value should not be inserted unless it is supported by the applicable current specification.
Nitisinone is not a stereochemically defined chiral API. PubChem's structure record does not identify stereogenic centers for the molecule.
Therefore:
Specific Rotation: Not applicable.
Enantiomeric Purity: Not applicable.
Stereochemical Purity: Not applicable.
Nitisinone API should be stored in a tightly closed container under controlled pharmaceutical storage conditions, protected from excessive heat, moisture and direct light as required by the applicable stability data and packaging specification.
The final commercial storage condition should be based on validated stability studies rather than applying a generic storage temperature.
| Parameter | Specification |
|---|---|
| Appearance | White crystalline powder or crystals |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |