Perphenazine is a synthetic phenothiazine derivative used as an antipsychotic pharmaceutical active ingredient. It belongs to the phenothiazine class and produces its principal pharmacological effects through antagonism of dopamine receptors in the central nervous system. It also possesses antiemetic activity. PubChem identifies Perphenazine as a phenothiazine antipsychotic, dopaminergic antagonist and antiemetic.
Perphenazine has the CAS Number 58-39-9, molecular formula C21H26ClN3OS, and molecular weight 403.97 g/mol. The same chemical identity and molecular weight are confirmed by NIST and the current USP-NF monograph.
Perphenazine is chemically identified as 4-[3-(2-chlorophenothiazin-10-yl)propyl]-1-piperazineethanol. Its structure contains a chlorinated phenothiazine nucleus linked to a piperazine-containing side chain. The molecular structure is responsible for its classification as a phenothiazine antipsychotic.
The API is a well-characterized small molecule with a molecular weight of 403.97 g/mol. The USP-NF monograph identifies Perphenazine under CAS 58-39-9 and specifies the molecular formula C21H26ClN3OS.
Perphenazine is used as an active pharmaceutical ingredient in formulations for the management of schizophrenia and other psychotic disorders, and it has also been used for the control of severe nausea and vomiting. Its pharmacological profile is primarily associated with dopamine receptor antagonism.
As an API, Perphenazine requires control of assay, organic impurities, moisture and inorganic residue. The current USP-NF monograph provides specific numerical quality requirements for these attributes.
The current USP-NF monograph defines Perphenazine as containing NLT 98.0% and NMT 102.0% of Perphenazine, calculated on the dried basis. Importantly, the USP assay is not an HPLC assay; the monograph uses direct potentiometric titration with 0.1 N perchloric acid in glacial acetic acid.
This distinction is important for your CMS because Perphenazine should not be listed as “Assay (HPLC) 98–102%” when describing the USP assay. The chromatographic LC method is used for organic impurities, while the official assay is titrimetric.
The USP organic-impurity procedure uses liquid chromatography with UV detection at 245 nm. The monograph specifically controls Perphenazine sulfoxide at NMT 0.20%, Perphenazine Related Compound B at NMT 0.50%, any individual unspecified impurity at NMT 0.10%, and total impurities at NMT 1.0%.
The USP chromatographic system uses an L7 column with a 30°C column temperature and a flow rate of 1.3 mL/min. System suitability requires a resolution of NLT 3.0 between Perphenazine and Related Compound B and a tailing factor of NMT 2.5.
The current USP monograph specifies Loss on Drying NMT 0.5%, determined by drying the sample under vacuum at 65°C for 4 hours. Residue on ignition is controlled at NMT 0.1%.
The monograph also specifies that Perphenazine should be preserved in tight, light-resistant containers.
| 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 0.10% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |