Terfenadine API is a synthetic H1-receptor antagonist and antihistamine belonging to the diarylmethane class. It was historically developed as a non-sedating antihistamine and marketed under brand names including Seldane. Terfenadine has since been withdrawn from the U.S. market because of its association with QT-interval prolongation and serious cardiac arrhythmias, particularly when metabolism was inhibited by certain drugs. FDA records identify terfenadine as a discontinued product, while regulatory sources document its historical use and subsequent replacement by fexofenadine.
For pharmaceutical and analytical purposes, terfenadine remains an established reference substance and is listed in pharmacopoeial reference-standard systems. The British Pharmacopoeia currently lists a quantitative terfenadine reference standard with CAS 50679-08-8 and a declared content of 99.8% for the current BPCRS lot.
Terfenadine has the molecular formula C32H41NO2 and molecular weight 471.67 g/mol. FDA's Global Ingredient Name Registry identifies terfenadine with a molecular weight of 471.67, while PubChem reports the same molecular formula and molecular weight.
The compound is a racemic substance containing stereogenic centers and is distinct from its active metabolite fexofenadine. Terfenadine is metabolized primarily through CYP3A4 to fexofenadine, which provides the principal antihistaminic activity.
| Property | Details |
|---|---|
| Product Name | Terfenadine |
| CAS Number | 50679-08-8 |
| Molecular Formula | C32H41NO2 |
| Molecular Weight | 471.67 g/mol |
| API Category | Antihistamine / H1-Receptor Antagonist |
| Pharmacological Class | Second-generation antihistamine |
| Appearance | White or almost white crystalline powder |
| Pharmacopoeial Reference | Ph. Eur. / BP |
| FDA UNII | 7BA5G9Y06Q |
The identity and molecular information are supported by FDA GINAS, PubChem and the British Pharmacopoeia reference-standard database.
Terfenadine was developed as a peripheral H1-receptor antagonist. Its pharmacological activity is closely associated with its conversion to fexofenadine, a selective peripheral H1-receptor antagonist. Terfenadine itself is a prodrug and undergoes extensive metabolism to fexofenadine.
Historically, terfenadine was used for the treatment of allergic conditions such as:
However, terfenadine is no longer marketed in the United States because of its cardiac safety risks. FDA-related documentation states that terfenadine was withdrawn worldwide during the 1990s because of the risk of cardiac arrhythmia and was superseded by fexofenadine.
Terfenadine has a formal Ph. Eur. monograph 0955, and the British Pharmacopoeia incorporates the pharmacopoeial requirements. The published monograph specifies content of 98.5–101.0% on the dried substance, loss on drying of NMT 0.5%, and sulfated ash of NMT 0.1%.
The related-substances procedure controls specified impurities A–J, with each specified impurity limited to NMT 0.2%, total impurities NMT 0.5%, and a disregard limit of 0.005%.
The pharmacopoeial assay is not an HPLC assay; it uses potentiometric titration with 0.1 M perchloric acid. Therefore, the CMS field "Assay (HPLC)" should be marked appropriately rather than incorrectly presenting the pharmacopoeial titrimetric assay as an HPLC specification.
Terfenadine API is a synthetic small-molecule pharmaceutical substance. Manufacturing controls should include appropriate raw-material controls, reaction monitoring, purification, crystallization, drying and analytical testing to ensure compliance with applicable pharmacopoeial or customer specifications.
A qualified Terfenadine API Manufacturer in India should maintain appropriate quality systems and provide batch-specific analytical documentation demonstrating identity, assay, related substances, drying loss and inorganic residue compliance.
The pharmacopoeial description identifies terfenadine as a white or almost white crystalline powder. It is very slightly soluble in water, freely soluble in methylene chloride, soluble in methanol and very slightly soluble in dilute hydrochloric acid. The substance exhibits polymorphism.
The pharmacopoeial identification includes a melting-point range of 146–152°C. TCI reports a product specification of 146–150°C, with a reference melting point of 148°C.
TCI reports water solubility of approximately 0.0963 mg/L at 25°C. This is a physicochemical reference value and should not be confused with a pharmacopoeial release specification.
The pharmacopoeial monograph specifies that terfenadine should be protected from light.
For bulk API, packaging should be selected to protect the material from light, moisture and contamination and should comply with the applicable stability and customer requirements.
A Terfenadine API supply package may include:
A reliable Terfenadine API Manufacturer in India should provide consistent quality, controlled manufacturing processes, validated analytical testing and complete batch documentation. Because terfenadine has a recognized pharmacopoeial standard, manufacturing and quality control can be aligned with the applicable Ph. Eur./BP requirements, including assay, related substances, loss on drying and sulfated ash.
| 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 0.1% |
| Individual Impurity | NMT 0.20% |
| Total Impurities | NMT 0.50% |
| Melting Point | 146–152°C |