Nefazodone Hydrochloride is a synthetic antidepressant active pharmaceutical ingredient (API) belonging to the class of serotonin modulators. It is a hydrochloride salt of nefazodone and has pharmacological activity involving serotonin receptors and serotonin reuptake.
Nefazodone is structurally related to the phenylpiperazine class of compounds and has a pharmacological profile that differs from conventional selective serotonin reuptake inhibitors (SSRIs). It acts primarily as a 5-HT2A receptor antagonist while also inhibiting serotonin reuptake.
Nefazodone Hydrochloride is used as a pharmaceutical active ingredient in the development and manufacture of oral antidepressant formulations.
Nefazodone Hydrochloride is a well-characterized small-molecule pharmaceutical API used in pharmaceutical formulation development, analytical research and quality-control applications.
The USP-NF contains a dedicated Nefazodone Hydrochloride monograph, confirming established compendial analytical requirements for the substance.
Important quality attributes include:
Product Name: Nefazodone Hydrochloride
CAS Number: 82752-99-6
Molecular Formula: C25H32ClN5O2 · HCl
Molecular Weight: 506.47 g/mol
Drug Class: Serotonin Modulator / Antidepressant
Therapeutic Class: Antidepressant
Therapeutic Area: Psychiatry / Central Nervous System
Molecule Type: Synthetic Small Molecule
The USP identifies Nefazodone Hydrochloride with the molecular formula C25H32ClN5O2·HCl and molecular weight 506.47 g/mol.
Nefazodone has a distinctive serotonergic mechanism involving both serotonin receptors and serotonin transport.
Its pharmacological actions include:
Nefazodone's mixed mechanism differentiates it from antidepressants that primarily inhibit serotonin reuptake.
Nefazodone Hydrochloride API is relevant to:
Nefazodone has been used as an antidepressant for the treatment of major depressive disorder.
Its regulatory status and availability vary by country. In the United States, nefazodone-containing products have had important safety considerations, particularly concerning severe liver injury, and its clinical use has consequently been restricted. Product-specific regulatory information should therefore be followed for the applicable market.
Nefazodone Hydrochloride is a pharmaceutical-grade crystalline solid. The API's physical characteristics, including particle size, crystallinity and moisture characteristics, can influence pharmaceutical formulation performance.
The final physical specification should be controlled according to the applicable compendial monograph or approved API specification.
A controlled Nefazodone Hydrochloride manufacturing process may involve:
The exact commercial manufacturing route should be based on the manufacturer's validated process and regulatory documentation.
Nefazodone Hydrochloride API quality control may include:
The USP monograph specifically provides analytical controls for assay and organic impurities.
The USP monograph specifies that Nefazodone Hydrochloride contains not less than 98.0% and not more than 102.0% of C25H32ClN5O2·HCl, calculated on the dried basis.
This makes 98.0%–102.0% a significantly stronger CMS value than a generic assumed API assay range.
The USP monograph identifies Nefazodone Related Compound A and Nefazodone Related Compound B as specified impurities.
The older official USP monograph gives the following acceptance criteria:
The USP has subsequently proposed/revised the organic-impurity presentation and reference-standard arrangements, so the current official USP-NF version should be checked when implementing the final CMS specification.
The official USP material specifies loss on drying of not more than 0.5%, using vacuum drying at 105°C for 3 hours.
The USP specification identifies residue on ignition NMT 0.1%.
The historical USP monograph specifies heavy metals at 0.001%. For a current commercial API specification, however, elemental impurities should be controlled according to the applicable current compendial requirements and ICH Q3D framework rather than automatically carrying forward an old heavy-metals test.
The USP monograph states that a 25 mg/mL solution in methanol meets the applicable completeness-of-solution requirement.
For website CMS purposes, it is safer to describe solubility as soluble in methanol rather than inventing a quantitative water-solubility value.
The historical USP monograph specifies preservation in tight containers and storage between 15°C and 30°C.
For a commercial product page, storage conditions should ultimately correspond to the current applicable API specification and validated stability data.
Nefazodone Hydrochloride is relevant to research involving:
| Parameter | Specification |
|---|---|
| Appearance | White crystalline powder or crystals |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 0.5% |
| Water Content | NMT 0.5% |