Phentolamine Mesylate is a synthetic alpha-adrenergic receptor antagonist used as a pharmaceutical active ingredient in cardiovascular and related therapeutic applications. It produces a relatively short-duration blockade of alpha-adrenergic receptors and causes vasodilation of vascular smooth muscle. The compound is particularly associated with the management of hypertensive episodes related to pheochromocytoma and with treatment of tissue injury following extravasation of certain vasoconstricting medicines.
Phentolamine Mesylate has the CAS Number 65-28-1 and is the monomethanesulfonate salt of phentolamine. The molecular formula is C17H19N3O·CH4O3S, commonly represented as C18H23N3O4S, with a molecular weight of 377.46 g/mol. The USP monograph identifies the substance under CAS 65-28-1 and specifies an assay of 98.0–102.0% on the dried basis.
Phentolamine Mesylate is chemically described as phenol, 3-[(4,5-dihydro-1H-imidazol-2-yl)methylamino]-, monomethanesulfonate. It is reported as a white or off-white, odorless crystalline powder. Official US product information states that it is freely soluble in water and alcohol and slightly soluble in chloroform. Its reported melting point is approximately 178°C.
The compound is a salt formed between phentolamine and methanesulfonic acid. Correct identification of the mesylate salt is important during API manufacturing because the salt form determines the molecular weight and analytical calculations.
Phentolamine is a non-selective alpha-adrenergic blocker. By antagonizing alpha-adrenergic receptors, it reduces catecholamine-mediated vasoconstriction and produces vasodilation. The resulting reduction in vascular resistance contributes to its antihypertensive activity.
Current product information identifies Phentolamine Mesylate Injection for prevention or control of hypertensive episodes associated with pheochromocytoma, as well as prevention or treatment of dermal necrosis and sloughing following certain norepinephrine extravasation events.
Phentolamine Mesylate has a USP drug-substance monograph. The current USP information specifies NLT 98.0% and NMT 102.0%, calculated on the dried basis. USP reference standards include Phentolamine Mesylate RS, Phentolamine Keto Analog RS and Phentolamine Related Compound A RS.
The USP 2025 compilation specifies Loss on Drying NMT 0.5%, with drying under vacuum at 60°C for 4 hours. It also specifies tight, light-resistant containers and storage at 25°C, with excursions permitted from 15°C to 30°C.
For impurity control, the current accessible USP compilation reports Phentolamine Keto Analog NMT 0.15%, Phentolamine Related Compound A NMT 0.15%, any unspecified impurity NMT 0.10%, and total impurities NMT 1.0%, with a reporting threshold of 0.05%.
Phentolamine Mesylate identification is supported by infrared spectroscopy, UV-visible spectroscopy and chromatographic retention time. The USP procedure includes UV detection at 232 nm for the chromatographic assay/impurity procedure.
The API should be evaluated for assay, related substances, moisture, residue on ignition and other applicable quality characteristics. A commercial USP specification from Spectrum Chemical additionally lists residue on ignition NMT 0.1% and sulfate NMT 0.2%. These values are useful for CMS specification purposes but should be distinguished from the core USP monograph requirements when applicable.
Phentolamine Mesylate is freely soluble in water and alcohol and slightly soluble in chloroform according to current US product information. It is a crystalline powder with a reported melting point of approximately 178°C.
Historical USP descriptive information reports that aqueous solutions are acidic to litmus, with a pH of about 5, but this is not equivalent to a formal numerical specification for a 1% solution. Therefore, the CMS 1% solution pH field should not incorrectly use the approximate descriptive value as a validated release specification.
| 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 0.1% |
| Individual Impurity | NMT 0.10% |
| Total Impurities | NMT 0.15% |
| Water Content | NMT 0.5% |