Tromethamine

• BPTrometamol
• Ph. Eur.Trometamol
• USP–NFTromethamine

Trometamol; Tris; THAM; tris(hydroxymethyl)aminomethane; Tris buffer; trometamolum

2-Amino-2-(hydroxymethyl)propane-1,3-diol · [77-86-1]

UNII 023C2WHX2V · PubChem CID 6503

C4H11NO3 · 121.14

pH adjuster, buffering agent

Typical concentrations: — · Dosage forms: Sterile (parenteral/ophthalmic)

Used as a buffering agent and pH adjuster in the range of about pH 7–9 in injections, including protein and mRNA vaccine products, and in ophthalmic, oral and topical preparations. It is also used to form water-soluble salts of acidic drugs (for example ketorolac, fosfomycin and dinoprost), as an emulsifier with fatty acids in cosmetic creams, and therapeutically as an intravenous alkalinising agent.

White or almost white crystalline powder or colourless crystals with a slight characteristic odour. It is a primary amine with three hydroxymethyl groups.

Melting point

168–172 °C

pKa

about 8.1 at 25 °C; it falls by about 0.03 unit per °C rise in temperature

Buffering range

about pH 7–9

Solubility

freely soluble in water; sparingly soluble in ethanol (95%)

pH

about 10.5 (0.1 M aqueous solution)

Stable. Aqueous solutions can be sterilised by autoclaving but absorb carbon dioxide from the air. Store in a well-closed container in a cool, dry place.

As a primary amine it reacts with aldehydes and ketones and can undergo Maillard reactions with reducing sugars. It may corrode copper, brass and aluminium, and reacts with acids.

Prepared by condensing nitromethane with formaldehyde in the presence of a base and reducing the resulting 2-nitro-2-(hydroxymethyl)propane-1,3-diol to the amine.

At the concentrations used as an excipient it is well tolerated. When given intravenously in therapeutic doses it can cause respiratory depression, hypoglycaemia and electrolyte disturbances, and extravasation of concentrated solutions damages tissue. It is excreted by the kidneys.

Observe normal precautions for the quantity handled. It is irritant to the eyes and skin; eye protection and gloves are recommended.

Included in the FDA Inactive Ingredient Database (intramuscular, intravenous and subcutaneous injections; ophthalmic, oral and topical preparations) and in parenteral and non-parenteral medicines licensed in Europe.

Tromethamine hydrochloride; trolamine; meglumine.

Because its pKa depends strongly on temperature, the pH of tromethamine buffers prepared at room temperature changes noticeably when refrigerated or warmed; buffers should be specified and checked at the intended temperature. A combination of tromethamine and its hydrochloride is commonly used to set pH precisely.