Pheniramine is a first-generation H1 antihistamine belonging to the alkylamine class of antihistaminic compounds. For pharmaceutical applications, it is commonly used in the form of Pheniramine Maleate, the maleate salt of pheniramine. Pheniramine Maleate is an established pharmacopoeial substance used as an antihistamine in pharmaceutical formulations.
Pheniramine Maleate has CAS No. 132-20-7, molecular formula C20H24N2O4, and molecular weight 356.42 g/mol. The USP-NF monograph identifies it as 2-[α-[2-dimethylaminoethyl]benzyl]pyridine bimaleate and specifies a content of 98.0–102.0% on the dried basis.
Pheniramine itself has the molecular formula C16H20N2, while the pharmaceutical maleate salt contains one maleate component, giving the overall formula C20H24N2O4. PubChem lists the free base as Pheniramine and the salt separately as Pheniramine Maleate.
Pheniramine Maleate is described in the BP 2025/Ph. Eur. monograph as a white or almost white crystalline powder, very soluble in water and freely soluble in ethanol 96%, methanol and methylene chloride.
Pheniramine acts primarily as a histamine H1-receptor antagonist and is used for its antihistaminic properties. It has been incorporated into pharmaceutical products intended for symptomatic relief of allergic conditions.
For API documentation, the exact salt form should be stated as Pheniramine Maleate, rather than simply Pheniramine, because the free base and maleate salt have different molecular weights and CAS numbers.
Pheniramine Maleate has current USP and BP/Ph. Eur. pharmacopoeial standards. The USP-NF monograph requires 98.0–102.0% Pheniramine Maleate calculated on the dried basis. The USP assay is performed by titration with 0.1 N perchloric acid, with 1 mL equivalent to 17.82 mg of Pheniramine Maleate. Therefore, the USP assay should not be incorrectly described as an HPLC assay.
The BP 2025/Ph. Eur. specification is tighter at 99.0–101.0% on the dried substance. Its assay is also potentiometric titration using 0.1 M perchloric acid.
The BP 2025/Ph. Eur. monograph provides specific numerical limits for the two named impurities:
The related-substances method uses liquid chromatography with UV detection at 264 nm.
The current USP presentation separately specifies chromatographic purity at NMT 0.5% for any individual impurity and NMT 2.0% for total impurities.
The USP melting range is 104–109°C, pH is 4.5–5.5 in a 10 mg/mL solution, loss on drying is NMT 0.5%, and residue on ignition is NMT 0.5%. Historical USP text also specifies heavy metals at 0.002% (20 ppm).
The BP 2025/Ph. Eur. standard specifies loss on drying NMT 0.5% and sulfated ash NMT 0.1%, providing a useful alternative pharmacopoeial specification set for API documentation.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.2% |
| Heavy Metals | NMT 20 ppm |
| pH (1% Solution) | 4.5–5.5 |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 0.5% |
| Melting Point | 104–109°C |