Histidine

• JPL-Histidine
• Ph. Eur.Histidine
• BPHistidine
• USP–NFHistidine

L-histidine; His; (S)-2-amino-3-(imidazol-4-yl)propanoic acid; α-amino-β-imidazolepropionic acid

(S)-2-Amino-3-(1H-imidazol-4-yl)propanoic acid · [71-00-1]

UNII 4QD397987E · PubChem CID 6274

C6H9N3O2 · 155.15

pH adjuster, buffering agent

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

Widely used as a buffer in biopharmaceutical formulations, particularly monoclonal antibodies for subcutaneous and intravenous use, typically at about 10–20 mM and pH 5.5–6.5 where the imidazole group buffers. It also acts as a stabiliser that reduces protein aggregation, as a cryo- and lyoprotectant in freeze-dried products, and as a nutrient in parenteral nutrition solutions.

White crystals or crystalline powder, odourless and with a slightly bitter taste. It is an essential amino acid; the pharmacopoeial material is the L-enantiomer.

pKa

≈ 1.8 (carboxyl), ≈ 6.0 (imidazole) and ≈ 9.2 (amino)

Isoelectric point

≈ 7.6

Melting point

decomposes at about 280 °C

Solubility

soluble in water (about 4 g/100 mL at 25 °C); very slightly soluble in ethanol

Buffer range

about pH 5.0–7.0

Stable as a solid; store in a well-closed container protected from light. In solution, histidine is susceptible to metal-catalysed and light-induced oxidation, and its degradation products can promote oxidation or discoloration of proteins. Solutions are usually prepared fresh or protected from light.

Chelates transition-metal ions such as copper, zinc and iron. Incompatible with strong oxidising agents; as an amine it can undergo Maillard reaction with reducing sugars.

Produced mainly by microbial fermentation, followed by isolation and purification by ion-exchange and crystallisation.

An essential dietary amino acid, regarded as non-toxic and non-irritant at the concentrations used as a buffer.

Observe normal precautions for the quantity handled; eye protection and gloves are recommended.

Included in the FDA Inactive Ingredient Database (intravenous and subcutaneous injections) and in parenteral medicines licensed in Europe, including many biological products.

Histidine hydrochloride monohydrate; arginine; glycine; methionine.

Histidine buffers are normally prepared from a combination of L-histidine and L-histidine hydrochloride monohydrate to reach the target pH without strong acids. The buffer pH of histidine changes noticeably with temperature, which should be considered for products stored refrigerated or frozen.