Phenoxybenzamine is a long-acting alpha-adrenergic receptor-blocking agent used primarily in the management of hypertension and sweating associated with pheochromocytoma. For pharmaceutical applications, the active ingredient is generally supplied as Phenoxybenzamine Hydrochloride, the hydrochloride salt of phenoxybenzamine.
Phenoxybenzamine Hydrochloride has the CAS Number 63-92-3, molecular formula C18H22ClNO·HCl, and molecular weight 340.29 g/mol. The USP defines Phenoxybenzamine Hydrochloride as containing 98.0% to 102.0% of phenoxybenzamine hydrochloride, calculated on the dried basis.
Phenoxybenzamine Hydrochloride is chemically known as N-(2-Chloroethyl)-N-(1-methyl-2-phenoxyethyl)benzylamine hydrochloride. It is described as a white to almost white crystalline powder. The current US product labeling reports a molecular weight of 340.29 g/mol and a melting range of 136–141°C.
Phenoxybenzamine itself, before salt formation, has CAS Number 59-96-1 and molecular formula C18H22ClNO. The pharmaceutical hydrochloride form is the more relevant API form for pharmaceutical applications.
Phenoxybenzamine produces long-lasting blockade of alpha-adrenergic receptors. This pharmacological activity reduces the effects of catecholamines on vascular smooth muscle and can lower blood pressure.
The US prescribing information states that Phenoxybenzamine Hydrochloride is indicated for the treatment of pheochromocytoma, particularly to control episodes of hypertension and sweating associated with catecholamine excess.
Phenoxybenzamine Hydrochloride has a current USP monograph. The USP specifies an assay range of 98.0–102.0% on the dried basis. Identification includes infrared spectroscopic identification and chromatographic retention-time comparison.
The current USP analytical procedure uses liquid chromatography with UV detection at 268 nm. The system suitability procedure specifically uses Phenoxybenzamine Nitrile as a reference impurity. The current monograph also recognizes Phenoxybenzamine Alcohol as a related impurity.
The USP numerical impurity requirements are particularly useful for CMS specifications. Phenoxybenzamine Alcohol is limited to NMT 0.10%, while any unspecified impurity is NMT 0.10% and total impurities are NMT 0.50%, with a reporting threshold of 0.05%. The USP impurity calculation excludes phenoxybenzamine aziridinium when present.
Phenoxybenzamine Nitrile is specifically used as a reference standard and system-suitability component in the current USP assay procedure.
Phenoxybenzamine Hydrochloride is freely soluble in ethanol and sparingly soluble in water. The official US labeling reports a melting range of 136–141°C. Independent US government toxicological data report water solubility of 15.2 mg/L at 25°C and a melting range of approximately 137.5–140°C.
The compound is sensitive to degradation under certain conditions. US government toxicological information describes it as unstable in neutral and alkaline solutions and sensitive to oxidation and photodegradation.
Phenoxybenzamine Hydrochloride is primarily relevant to pharmaceutical development involving alpha-adrenergic blockade and pheochromocytoma treatment. Its long-lasting receptor-blocking activity distinguishes it from shorter-acting alpha-blocking agents.
For API quality control, the most important verified numerical attributes include the 98.0–102.0% assay range, 0.10% limit for Phenoxybenzamine Alcohol, 0.10% limit for any unspecified impurity, and 0.50% total impurity limit. These values are preferable to generic specification-dependent placeholders because they are supported by the USP monograph.
| 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 0.10% |
| Total Impurities | NMT 0.50% |
| Water Content | NMT 0.5% |